Microtubule plus-end loading of p150Glued is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells

Watson, Peter; Stephens, David

doi:10.1242/jcs.02999

Cited by 100 publications

(94 citation statements)

References 41 publications

(84 reference statements)

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“…A second possibility (not mutually exclusive with the first) is that the two CAP-Gly domains endow CLIP-170 with the ability to bind simultaneously to tubulin and other CAP-Gly-binding proteins. One such protein is EB1 (18,35). Interestingly, it has been reported that EB1 has a higher affinity for CAP-Gly-1 than CAP-Gly-2 (33).…”

Section: Discussionmentioning

confidence: 99%

Minimal Plus-end Tracking Unit of the Cytoplasmic Linker Protein CLIP-170

Gupta

Paulson

Folker

et al. 2009

Journal of Biological Chemistry

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Cytoplasmic linker protein 170 (CLIP-170) is the prototype microtubule (MT) plus-end tracking protein (؉TIP) and is involved in regulating MT dynamics. A comprehensive understanding of the process by which CLIP-170 tracks MT plus ends would provide insight into its function. However, the precise molecular mechanism of CLIP-170 ؉TIP behavior is unknown, and many potential models have been presented. Here, by separating the two CLIP-170 CAP-Gly domains and their adjacent serine-rich regions into fragments of varied size, we have characterized the minimal plus-end tracking unit of CLIP-170 in vivo. Each CLIP-170 fragment was also characterized for its tubulin polymerization activity in vitro. We found that the two CAP-Gly domains have different activities, whereas CAP-Gly-1 appears incompetent to mediate either ؉TIP behavior or MT nucleation, a CLIP-170 fragment consisting of the second CAPGly domain and its adjacent serine-rich region can both track MT plus ends in vivo and induce tubulin polymerization in vitro. These observations complement recent work on CLIP-170 fragments, demonstrate that CAP-Gly motifs do not require dimerization for ؉TIP and polymerization-promoting activities, and provide insight into CLIP-170 function and mechanism.

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Section: Discussionmentioning

confidence: 99%

Minimal Plus-end Tracking Unit of the Cytoplasmic Linker Protein CLIP-170

Gupta

Paulson

Folker

et al. 2009

Journal of Biological Chemistry

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“…Both EB1 family proteins and XMAP215 can act independently as microtubule growth promoters, but in some instances they are linked by SLAIN motif family proteins, which strongly stimulate processive microtubule growth in interphase cells [van der Vaart et al, 2011]. The dyneindynactin complex can also access microtubule ends in both EB1-dependent and independent manners [Miller et al, 2006;Watson and Stephens, 2006]. It is noteworthy that n 608…”

Section: Molecules Involved In Microtubule End Positioningmentioning

confidence: 99%

Shaping microtubules into diverse patterns: Molecular connections for setting up both ends

Mimori-Kiyosue¹

2011

Cytoskeleton

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Microtubules serve as rails for intracellular trafficking and their appropriate organization is critical for the generation of cell polarity, which is a foundation of cell differentiation, tissue morphogenesis, ontogenesis and the maintenance of homeostasis. The microtubule array is not just a static railway network; it undergoes repeated collapse and reassembly in diverse patterns during cell morphogenesis. In the last decade much progress has been made toward understanding the molecular mechanisms governing complex microtubule patterning. This review first revisits the basic principle of microtubule dynamics, and then provides an overview of how microtubules are arranged in highly shaped and functional patterns in cells changing their morphology by factors controlling the fate of microtubule ends. V C 2011 Wiley Periodicals, Inc.

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“…In addition, dynactin plays other roles independently of microtubule motors, by facilitating attachment of microtubules to several subcellular structures. Although initial studies demonstrated that dynactin contributed to microtubule anchoring at the centrosome during interphase (15,16), recent results provided the first clues concerning its role as an initial receptor for cytoplasmic membrane vesicles at microtubule plus ends (17)(18)(19)(20), although this model has been brought into question (21).…”

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confidence: 99%

Molecular and Functional Basis for the Scaffolding Role of the p50/Dynamitin Subunit of the Microtubule-associated Dynactin Complex

Jacquot

Maidou-Peindara

Bénichou

2010

Journal of Biological Chemistry

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p50/dynamitin (DM) is a major subunit of the microtubuleassociated dynactin complex that is required for stabilization and attachment of its two distinct structural domains, namely the Arp1 rod and the shoulder/sidearm. Here, we define the determinants of p50/DM required for self-oligomerization of the protein and for interactions with other subunits of the dynactin complex. Whereas the N-terminal 1-91-amino acid region of the protein is required and sufficient for binding to the Arp1 rod, additional determinants contained within the first half of the protein are required for optimal recruitment of the p150Glued subunit of the shoulder/sidearm. Overexpression experiments confirmed that the N-terminal 1-91-amino acid region of p50/DM is critical for dynactin functionality, because this fragment acts as a dominant negative to inhibit both dynein-dependent and -independent functions of the complex. Furthermore, the first two predicted coiled-coil motifs of p50/DM contain determinants that mediate selfassociation of the protein. Interestingly, p50/DM self-association does not contribute to p50/DM-induced disruption of the dynactin complex, but most likely participates in the stabilization of the complex.The dynactin complex was initially identified as a multiprotein complex co-purifying with the minus-end-directed microtubular motor dynein and capable of activating membrane vesicle movements (1, 2). Initial genetic studies performed in yeast, filamentous fungi, and Drosophila demonstrated that dynactin was an obligate cofactor of the dynein motor (3-6). To date, many functional studies confirmed that the dynactin complex is required for most, if not all, dynein-based cellular processes (reviewed in Ref. 7). During interphase, dynactin plays a major role in all dynein-based motile events by providing both stable cargo binding and processivity activities, to ensure proper vesicular transport between cellular compartments along the microtubules (8 -11). Moreover, the dynactin complex was also shown to interact with and increase the processivity of the kinesin-II plus-ended motor, suggesting an unexpected role in plusend-directed motile events (12)(13)(14). In addition, dynactin plays other roles independently of microtubule motors, by facilitating attachment of microtubules to several subcellular structures. Although initial studies demonstrated that dynactin contributed to microtubule anchoring at the centrosome during interphase (15, 16), recent results provided the first clues concerning its role as an initial receptor for cytoplasmic membrane vesicles at microtubule plus ends (17-20), although this model has been brought into question (21).Dynactin is a multiprotein complex of ϳ1.2 MDa, composed of 11 different polypeptides that are present as single or multiple copies and organized in two distinct structural domains (see Fig. 1) as follows: (i) the Arp1 rod, consisting of a short polymer of eight copies of Arp1 (actin-related protein-1), capped on its positive barbed end by the CapZ ␣/␤ heterodimer and on its nega...

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Microtubule plus-end loading of p150Glued is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells

Cited by 100 publications

References 41 publications

Minimal Plus-end Tracking Unit of the Cytoplasmic Linker Protein CLIP-170

Minimal Plus-end Tracking Unit of the Cytoplasmic Linker Protein CLIP-170

Shaping microtubules into diverse patterns: Molecular connections for setting up both ends

Molecular and Functional Basis for the Scaffolding Role of the p50/Dynamitin Subunit of the Microtubule-associated Dynactin Complex

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