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Cell Motility and the Cytoskeleton 35:85-93 (1996)
Views and Reviews
Making a Connection: The “Other”
Microtubule End
Michael P. Koonce
Division of Molecular Medicine, Wadsworth Center, and Department of
Biomedical Sciences, State University of New York, Albany, New York
INTRODUCTION
A recent congruence of structural, biochemical,
and molecular genetic work has identified a likely candidate for the long sought centrosomal component that
nucleates and anchors the minus ends of microtubules in
many eukaryotic cells [Moritz et al., 1995; Zheng et al.,
19951. This important work will no doubt lead to a better
understanding of where the microtubule cytoskeleton
comes from and its regulation throughout the cell cycle.
However, determining the morphogenetic events behind
establishing and maintaining the spatial patterns of microtubules in interphase and dividing cells are separate
and equally important issues. There is no doubt that the
dynamic nature of microtubules plays a major role in
providing a constant supply of polymer from the centrosome. But, to what extent do interactions at the
“other” microtubule end contribute to the overall pattern
of this cytoskeletal component?
The seminal paper by Kirschner and Mitchison
that, in 1986, ushered in a new era of thinking about
microtubules and the cytoskeleton elaborated the idea of
“capping structures near the cell periphery” that bind
and selectively stablize the microtubule plus ends. If appropriately regulated, this could lead to a morphogenetic
differentiation of the microtubule network and overall
cell shape. While the kinetochore region of condensed
chromosomes has served as a paradigm for such structures, a number of molecules and events have now been
identified that could participate in maintaining other arrays of microtubules. This review examines what is
known about structural interactions at or near the plus
ends of microtubules, and how these would contribute to
the spatial organization of a cellular array. The primary
focus here is on interphase microtubules [for recent reviews of morphogenetic events in mitotic spindle assembly, see McIntosh, 1994; Inoue and Salmon, 1995; Hyman and Karsenti, 19961.
0 1996 Wiley-Liss, Inc.
The Spatial Microtubule Pattern is
Actively Maintained
In a generic eukaryotic cell, the interphase microtubule network primarily functions to organize the cytoplasmic membrane systems [Cole and LippincottSchwartz, 19951. It helps direct endo- and exocytotic
trafficking of vesicles between the endoplasmic reticulum (ER), Golgi, plasma membrane, and lysosomes. It
further organizes the Golgi membranes as well as the
position of the endoplasmic reticulum and other membrane-bound organelles. The microtubule polarity (minus ends anchored at the centrosome, plus ends distal)
provides direction for motor molecule activity, and the
dynamic radial pattern provides access to all regions of
the cell [e.g., Holy and Liebler, 19941. Most microtubules probably function as a support for organelle motility. Further, it is generally assumed that in a radial pattern, each microtubule acts independent of its neighbor.
In specialized cell processes where structural support is
required (e.g., axons, dendrites, and kinetochore fibers),
the microtubules are bundled together for stability and
rigidity, and their removal with nocodazole profoundly
affects the processes structure.
There are at least three components to the architecture of a given microtubule array. First is the association
of the microtubule at its organizing center. A y-tubulincontaining ring complex has been found in Drosophilu
and Xenopus that serves as a nucleating template to anchor the minus ends in the centrosome [Moritz et al.,
1995; Zheng et al., 19951. Given that nearly all eukaryotic cells maintain some form of a microtubule-organizing center and that y-tubulin stains positive in many of
Received May 22, 1996; accepted June 10, 1996
Address reprint requests to Dr. Michael Koonce, Wadsworth Center,
Empire State Plaza, PO Box 509, Albany, NY 12201-0509.
86
Koonce
these structures, it is tempting to speculate that these ring
complexes will be conserved. This will no doubt be addressed experimentally within the next few years. Although some cell fragments can form aster-like arrays in
the absence of a conventional centrosome, these are
likely due to the aggregation of microtubule ends and
associated components to form a short term, centrosomelike structure [McNiven and Porter, 1988; Maniotis and
Schliwa, 19911. In vitro work suggests that this could be
assembled in large part by a dynein-like motility [Verde
et al., 19911. The second architecture component is the
dynamic character of the polymer. This is in part due to
the microtubule’s inherent structural instability and in
part to modifications imposed by associated proteins and
post-translational modifications. Dynamics do play an
important role in vivo since forced polymerization and
stabilization with tax01 results in disorganized arrays and
bundles. These structures do not appear over time to
resolve themselves into an aster. Third, in order for the
microtubule system to be functional, there must also be
distal interactions of the polymer with other cellular
structures, be that a second or third microtubule in a
bundle, or a vesicle, membrane, or other protein. As
discussed below, these distal interactions are critical for
determining and maintaining the overall form of the microtubule network.
In many active cells, the centrally focused, radial
microtubule array is maintained as movement or shape
change occurs [Schliwa and Honer, 19931. In some cells,
rearrangement of the microtubule network can precede
cell movement, suggesting that there are active forces
that sense and govern its spatial pattern. It is unlikely
that microtubule dynamics alone could account for these
rapid rearrangements. Instead, distal interactions of the
polymer with organelles or the cell cortex are probably
necessary to anchor or generate a force along the polymer to connect microtubules to the cytoplasm. As shape
changes occur, these connections help maintain the radial pattern and cell polarity. Indeed, there are several
examples in the literature which demonstrate that forces
acting along the sides or from the ends of microtubules
can be strong enough to move a microtubule array
through the visoelastic cytoplasmic matrix [Lutz et al.,
1988; Hyman, 1989; Palmer et al., 1992; Waters et al.,
19931. Recent work from our laboratory [Koonce and
Sams6, 19961 suggests that by overexpressing the head
domain of a cytoplasmic dynein in Dictyostelium, the
microtubule network appears uncoupled from its cytoplasmic anchorage. In this work, many interphase cells
no longer have a radial array of microtubules. Instead the
microtubules appear loosely bundled around the nucleus
(Fig. 1). While initial microtubule regrowth from centrosomes following nocodazole treatment appears similar
to wild-type cells, these radial patterns are not main-
tained in cells expressing the truncated dynein. These
data further argue that there are distal connections to the
microtubules that are necessary to keep the pattern radial.
Where Would a Distal Anchor Lie?
Distal microtubule anchors could act in at least
three sites to control overall pattern and dynamics: (1) at
the very tip of the polymer, (2) anchored in the cell
cortex and interacting with the side of the polymer at or
near its end, or (3) existing as the sum of all protein and
organelle interactions along the length of the polymer.
Tip anchors. Two of the best characterized tip
anchors are found at the ends of axonemal microtubules
in cilia and flagella, and at the kinetochore in dividing
cells [for reviews of kinetochore-microtubule interactions, see Murray and Mitchison, 1994; InouC and
Salmon, 1995; Hyman and Karsenti, 19961. Capping
structures that appear to plug the ends of the doublet and
central pair microtubules of axonemes and link these
structures to the plasma membrane have been observed
in a variety of organisms (reviewed in Dentler, 1990).
One of these structures has been characterized in some
detail as a large multisubunit complex of 1,500-2,OOO
kDa [Wang et al., 19931. A 97-kDa component of this
complex shares antibody reactivity with a polypeptide(s)
located at the kinetochores of some mitotic chromosomes, leading to the interesting suggestion that these
two structures share some conserved function [Miller et
al., 19901. Axonemal caps may function to regulate assembly or stability of the core microtubule structure, or
they may play a role in coordinating the motility of cilia
or flagella. A cytoplasmic equivalent complex that plugs
individual microtubules and links them to the membrane
has not (yet) been described. However, interphase extracts of Xenopus eggs contain ER-derived vesicles that
favor connection to microtubule tips in vivo [WatermanStorer et al., 19951. If these vesicles were part of extensive membrane systems in situ then assembly/disassembly reactions of the microtubule polymer could be
sufficient to generate a tip force or a transient cytoplasmic anchor [e.g., InouC and Salmon, 1995; Lombillo et
al., 1995a,b]. Additionally, the cortical bud site in S.
cerevisiue may be in part an analogous structure [Lew
and Reed, 19951. During cell division, the bud site interacts with astral microtubules and plays an anchorage
role in determining the spindle position [Palmer et al.,
19921.
Cell cortex anchor. There are several examples of
specialized cortical areas that interact with microtubules
in meaningful ways. The term cortex here is meant to
describe the nebulous region between the plasma membrane and the organelle-filled portion of the cytoplasm.
In many cells this region is filled with an actin-rich fil-
Microtubule Connections
87
Fig. 1. Dictyostelium amoeba visualized with a tubulin antibody
(A,C) and corresponding phase contrast (B,D). A,B show a wild type
AX-2 Dictyostelium cell. Note the radial microtubule pattern typical of
most AX-2 cells and of most eukaryotes. C,D show one example
typical of transformed AX-2 cells that overexpress a 380-kDa head
domain fragment of the dynein heavy chain. Here the microtubule
array has lost its radial character and appears whorled around the
nucleus. We favor the idea that this morphology results from microtubules having lost their distal cellular connections so that as cells
move, the array becomes compressed around the nucleus. See text and
Koonce and SamsB [1996] for more details. Scale bar = 10 pm.
arnent meshwork which may act as a physical barrier to
microtubules. During oogenesis and early development,
interactions of astral microtubules with the cell cortex are
important for positioning and anchoring of some spindles
[Strome, 1993; Ault and Rieder, 1994; Karsenti et al.,
19961. In Xenopus, a massive parallel layer of microtubules transiently forms near the interface between the
cortex and interior shortly after fertilization. This layer
directs a cortical rotation necessary to establish the dorsaVventra1 axis of the embryo [Elinson and Rowning,
1988; see also Larabell et al., 19961. When helper
T-cells encounter their appropriate target [Geiger et al.,
19821 and in epithelial cells activated to move by wounding of a monolayer [Kupfer et al., 1982; Gotlieb et al.,
1983; Euteneuer and Schliwa, 19921, the microtubule
array appears stimulated by a cortical-related event to
polarize the cell in the direction in which movement will
occur. Recent work with T-cells has correlated a signaling cascade identified in yeast with the regulation of the
cytoskeletal rearrangements involved with activation
[Stowers et al., 19951.
Many cortical interactions have not been directly
demonstrated but can be well-inferred by subsequent
events. For example, during neuronal cell differentiation, microtubule bundles fill and support the growing
axons and dendrites. The initial recruitment events that
bundle microtubules behind the nascent growth cone are
not well understood but likely involve stabilization directed in part by a localized cortical activity. Conidia
germination in some fungi (Aspergillus, Neurospora)
produces an elongating tube (hypha) into which nuclei
migrate and assume evenly spaced positions [Morris et
88
Koonce
Fig. 2. Network extension in Reticulomyxa. Two examples of cell
processes growing from the cell body. The video-processed phase
contrast images show microtubule bundles extending to the tips of
these reticulopodia (arrowheads). Despite a rapid rate of growth, microtubules are nearly always found in association with the ends of
growing and branching tubes. Scale bar = 5 km.
al., 19951. Microtubules are essential for this motility
and bundles extend into a phase-dense matrix at the hypha end. Although the polarity of the microtubules between the last nuclear-associated MTOC and the hypha
end is not known, the event that specifies the site of
conidia outgrowth likely involves an initial and subsequently maintained microtubule-cortex interaction. In a
similar but extreme case, colinear bundles of microtubules and microfilaments support network extensions
from the cell body of the freshwater amoeba, Reticulomyxa [Koonce et al., 19861. In these structures, which
can extend at rates in excess of 100 km/min, dense bundles of microtubules maintain connections at or near the
growing tip. These often terminate in a phase-dense
plaque (Fig. 2). The microtubules provide structural support and serve to transport growth components to the
ends. To what extent this phase-dense plaque resembles
the structures seen in hyphal tubes or analogous components in neurons remains to be determined. Nevertheless, these structures appear to coordinate assembly (and/
or sliding) and bundling of microtubules with process
growth.
Summation anchor. Integration of all the motordriven movements along the length of a microtubule
would generate a large viscous drag. This alone would
provide a substantial “sea anchor” for the polymer in the
face of local cytoplasmic movements. If some of these
motor-driven movements were connected to additional
cytoplasmic elements, further tension could be placed on
the polymer. Work by Hiramoto [ 19861 using a focused
UV light to locally inactivate the microtubule poison
colcemid resulted in a polarized growth of microtubules
from the centrosome. The resulting partial aster moved
in the direction of polymer growth, suggesting that a
substantial pulling force exists on the microtubule system. In a complete microtubule array this force would be
radially balanced. While no net translocation would occur, the whole system should be under tension. The site
of force production here is not known, but either a kinesin-like activity at the MTOC or a dynein-like activity
Microtubule Connections
in the cytoplasm could produce the same effect. In another example, kinesin is believed to be at least partially
responsible for extending the intermediate filament network in some cells [Gyoeva and Gelfand, 19911. At
some point a balance must be reached between the extensile force of a kinesin molecule and the elastic force of
the intermediate filament network. If the cortex anchors
the microtubule ends, then the two cytoskeletal systems
could be linked under tension into a tensegrity-like structure.
A number of structural MAPShave been characterized that bundle microtubules (MAP-2, tau, etc.), others
bind the polymer side and presumably regulate dynamics
[reviewed in Mandelkow and Mandelkow, 19951. Still
other MAPS are believed to connect microtubules to cytoplasmic components, either providing structural links
or localize proteins, enzyme complexes, RNAs, etc. One
type of cytoplasmic linker protein (CLIP- 170) has been
characterized in some detail to couple microtubules and
endosome vesicles. Interestingly, this binding seems to
favor a subset of microtubules, and at peripheral positions near their plus ends [Rickard and Kreis, 19901.
This activity may serve a prerequisite step for binding
motor molecules or may serve as a cytoplasmic anchorage. A recent review describes several motifs in this
protein that are shared with other microtubule-related
polypeptides, suggesting they may constitute a family of
related activities [Rickard and Kreis, 19961.
Molecular Connections
As the preceding sections illustrate, several mechanisms exist to “connect” the microtubules to the cytoplasm. In doing so, they either maintain polarity important for directional activities (polarized transport or
secretion) or could be used to establish an asymmetry
important for division or differentiation. The three categories are not mutually exclusive: complexes bound to
the microtubule tip may also exert a force near the polymer end (as in the case for a kinetochore). In some instances, clear cortical connections between the plasma
membrane and microtubule can be seen all along the
polymer length (as in cilia and flagella). The structural
linkages are also likely to be modulated by a regulatory
system that can sense the microtubule requirements of a
given cell activity.
Several components and mutations have recently
been described that appear important in maintaining the
overall microtubule pattern and act at a site distal from
the centrosome. These are summarized in Table I. Some
of these may form part of structural complexes, others
are motor protein components that may also provide a
structural role. Two of the more general themes emerging from these data are that cytoplasmic dyneins play
important roles in anchoring the peripheral ends of mi-
89
crotubules and that there is an intimate relationship between the microtubule and actin filament-based cytoskeletal systems.
Cytoplasmic dynein-like activity has long been implicated to provide a traction force along the microtubule
polymer. If anchored in the cortex, it has the proper
polarity of movement to interact with and pull on the
peripheral microtubule ends. If uniformly positioned
throughout the cortex, transient activity would reinforce
the radial interphase array. Alternatively, if dynein activity was coupled to cortex-generated signals, it could
be manipulated to engage a subset of microtubules and to
reorient the microtubule organizing center. Although dynein antibodies do not dramatically localize this protein
to the cortex of many cells, small functional amounts at
the cell periphery would be difficult to distinguish above
the greater, soluble, cytoplasmic pool. Some areas of
focused microtubule-cortex interaction do show dynein
localization [Xiang et al., 1995b; Yeh et al., 19951, lending support for a general cortical anchor role. Mutations
and manipulations of the dynein heavy chain gene and
related components are also consistent with a corticalbased function. Dynein’s role here does not necessarily
require processive force generation. It could provide an
anchor function by acting as an ATP-sensitive coupler
that in turn is pulled on by microtubule-based motor
proteins located elsewhere on the polymer.
Another intriguing aspect of microtubule organization lies in its relationship with the actin filament network. The actin filament machinery provides the basic
locomotive force for cell movement and shape. While
not necessary for movement, microtubules maintain the
cytoplasmic organization necessary to direct growth
components and provide structural support [Schliwa and
Honer, 19931. Thus, microtubules are important for persistent, directed locomotion and differentiation. It seems
reasonable to expect that the two filament systems share
a common machinery that coordinates their interaction.
It has been known for some time that physical connections exist between the two filament systems [e.g.,
Schliwa and van Blerkom, 19811. More recent demonstrations that individual vesicles can move on either substrate [Langford, 19951 and that perturbations of regulatory components can affect both microtubule and
microfilament organizations [Chen et al., 1994; Ursic et
al., 1994; Guo and Kemphues, 1995; Stowers et al.,
19951 emphasize the biochemical connections between
these two assemblies. Furthermore, these observations
highlight motor-molecule activity as one avenue for
crosstalk. Vesicles containing myosin, dynein, and kinesin activities on their surface potentially serve as dynamic force-producing crosslinkers to connect the two
filament systems. In addition, disruption of the actinrelated component of dynactin, the molecular complex
Koonce
90
TABLE I. Connections to the Distal Ends of Microtubules (MTs)
~~
STRUCTURAL
Cytoplasmic dynein and related oroteins
Dynein heavy chain (DHC) Minus end directed organelle motor. In yeast and other fungi, possible cortical-attached MT anchor for
cytoplasmic and mitotic astral MTs [Eshel et al., 1993; Li et al., 1993; Plamann et al., 1994; Xiang et
al., 19941. Essential in Drosophila [Gepner et al., 19961 and Dictyosteliurn [Koonce et al., 19941, and
participates in bipolar spindle formation in some mammalian cells [Vaisberg et al. , 19931.
Dynein light chain
8-kda subunit, nudG locus in Aspergillus [Beckwith and Moms, 19951. Mutations abolish dynein
localization at growing hyphal tip and produce a phenotype similar to mutations in the heavy chain.
Dynactin
Multi subunit complex, potential receptor/anchor for cytoplasmic dynein [Schroer, 1994; Schroer et al.,
1996; Vallee and Sheetz, 19961.
p 150G'"ed
Links dynactin to DHC via interaction with dynein intermediate chain [Vaughan and Vallee, 19951. Also
has regulated MT-binding activity. Shares some domain homology with CLIP-170 [Rickard and Kreis,
19961.
Actin-related protein
Strikingly similar phenotype as dynein heavy chain mutations in yeast and filamentous fungi [Clark and
Meyer, 1994; Muhua et al., 1994; Plamann et al., 1994; Schroer, 1994; Schroer et al., 19961.
JNM- 1
44-kDa budding yeast protein [McMillan and Tatchell, 19941. Mutants show a nuclear migration
phenotype very similar to DHC mutations. Potential anchor component for astral MTs in bud site.
NUMlp
Cortex-associated 3 13-kDa budding yeast protein believed to interact with astral MTs to align the nuclear
spindle [Farkasovsky and Kuntzel, 19951.
BIK 1
60-kDa budding yeast polypeptide that colocalizes with MTs [Berlin et al., 19901. Mutants show aberrant
localization of spindle during mitosis and abnormal cytoplasmic MT morphologies. Shares some
domain homology with CLIP-170 [Rickard and Kreis, 19961.
CLIP- I70
Cytoplasmic-linker protein from humans [Rickard and Kreis, 19901; 170-kDa MT-binding protein that
favors a subset of plus ends. It is believed to mediate linkages between endocytotic vesicles and MTs.
May also facilitate docking of motor protein for vesicle movement. Shares domain homology with
pl5OGIuedand BIKl, suggesting that there may be a conserved family of such linkers [Rickard and
Kreis, 19961.
MT-membrane attachments
This is a vast field. However, one demonstration of note is the association of the RER with MTs in vitro,
mediated by globular domains enriched with active MT motors [Allan and Vale, 19941.
MT-capping proteins
Axoneme complex
Membrane-associated MT plugs. Large, multisubunit complex [Miller et al., 1990; Wang et al., 19931.
TACs
Membrane-MT tip attachement complexes in interphase-arrested Xenopus egg extracts [Waterman-Storer
et al., 19951.
Motor protein-mediated
Some (but not all) MT-based motor proteins can couple latex microspheres to the ends of shrinking MTs
[Lombillo et al., 1995a,b]. Though this was demonstrated with components assembled in vitro,
analogous mechanisms may be employed in the TACs mentioned above, and in kinetochores during
cell division.
MDMl
5 1-kDa budding yeast intermediate filament-like protein [McConnell and Yaffe, 19921. Deletions affect
mitochondria distribution and mitotic spindle position. Could act as a structural scaffold to orient
microtubule-based motilities.
Axonemal kinesin
Kinesin-related protein forms a motile "raft" that appears to connect plasma membrane components to
the sides of the axonemal MTs [Kozminski et al., 19951.
REGULATORY
CDC-42
Small ras-like GTPase involved in signal transduction [Stowers et al., 19951. Deletion affects both
actin-membrane interactions and ability of cells to orient MT array. Homologs found in several
organisms.
PAR- 1
126-kDa C. elegans serinelthreonine protein kinase [Guo and Kemphues, 19951. Polarized cortical
location in early embryos. Mutations affect p-granule partitioning and mitotic spindle orientation.
Homologs found in several organisms.
nudF
49-kDa Aspergillus polypeptide related to the @-subunitof heterotrimeric G-proteins [Xiang et al.,
1995al. Deletion causes a phenotype indistinguishable from mutations in the dynein heavy chain. This
component may help regulate dynein's role in MT-based nuclear migration.
TCP-1lBin 2pIBin 3pIANC2
Related family of polypeptides that share homology with chaperonins [Chen et al., 1994; Ursic et al.,
1994; Vinh et al., 19941. When mutated in yeast, they affect both MT and actin filament structure and
associated processes.
Microtubule Connections
believed to anchor dynein on vesicles in the cytoplasm
[Schroer, 1994; Vallee and Sheetz, 19961, can produce
the same phenotype as dynein heavy chain mutations.
Given its sequence relationship to actin, this component
may provide a link between dynein and the microfilament system and thus provide the firmest association
between the microtubules and the cortical meshwork of
actin filaments [see also Schroer et al., 19961.
Review and View
Linking the “other” microtubule end to the cytoplasm is one mechanism by which a cell controls the
spatial pattern of its microtubule array. Distal connections can act to modify microtubule dynamics and produce a viscous drag that contributes to the elastic nature
of the cytoplasm. In addition, there are numerous examples that demonstrate an intimate association of the microtubules with the cell cortex. If these linkages were
coupled with cortical regulatory machinery, a mechanism would be created that enables cells to transduce
extracellular signals into intracellular architectural
changes that specify cell polarity and function. The componentdevents outlined in Table I likely represent the
initial players of complex interactions and regulation;
genetic and biochemical analyses will no doubt uncover
many more [e.g., Verdeetal., 1995; Brunoetal., 19961.
It is interesting to compare these interactions with microtubule-kinetochore connections formed during division. The kinetochore is a small structure that assembles
onto the primary constrictions of condensing chromosomes and functions, in part, to capture microtubule plus
ends and produce force. Its activity is temporally regulated, probably by multiple mechanisms. The cortical
surface of a cell could be viewed as a “diffuse kinetochore,” that is, a regulated machine that can engage the
distal ends of microtubules and produce force. Unlike
the chromosomal kinetochore, components could be continuously mantained over the entire cell cortex. If these
components were normally turned “off,” they would
not interfere with microtubule dynamics or vesicle trafficking. In addition, they may not normally be detected
unless a cell is stimulated to move or differentiate. Regulation, either through a global activation, or local interactions dictated by intra- or extracellular cues, could
activate cortex components to engage underlying microtubules and produce a force/anchorage. This exertion
could stabilize the local polymers, and thus provide a
structural anchor, and target a transport direction for exo/
endocytosis of membrane-bound components. Cytoplasmic dynein, the dynactin complex, and a ciliary capping
protein localize to some mitotic kinetochores and may
provide a cortical anchor in interphase cells [Miller et
al., 1990; Vallee and Sheetz, 1996; Schroer et al., 19961.
Thus, there is some evidence to suggest that a common
91
machinery can be shared between kinetochores and the
cell cortex. As additional components are characterized,
it may be interesting to see whether this comparison
holds up.
ACKNOWLEDGMENTS
We thank Drs. Alexey Khodjakov, Jeff Ault, and
Conly Rieder for stimulating discussions on this topic.
The data for Figure 2 were obtained while M.P. Koonce
was a graduate student in Dr. Manfred Schliwa’s laboratory. The work in our lab is supported in part by the
NIH (GM51532) and in part by institutional support from
the Wadsworth Center.
NOTE ADDED IN PROOF
Two additional microtubule-binding proteins have
come to our attention: Gephyrin, a 93 kDa polypeptide
appears to link glycine receptor function with microtubules located at synapses [Prior et al., Neuron 8: 11611170, 19921, and adenomatous polyposis coli (APC), a
3 10 kDa tumor supressor protein appears to bind a subset
of microtubule ends and may link these to cadherin junctions involved with active cell migration in epithelial
cells [Nathke et al., J. Cell Biol. 134:165-179, 19961.
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