Cell Cycle Control of Kinesin-Mediated Transport of Bik1 (CLIP-170) Regulates Microtubule Stability and Dynein Activation

Carvalho, Pedro; Gupta, Mohan L.; Hoyt, M. Andrew; Pellman, David

doi:10.1016/j.devcel.2004.05.001

Cited by 213 publications

(285 citation statements)

References 65 publications

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“…This suggests that these interactions may represent a conjugation event between the AD-SMT3 and the KAR9-BD and/or BIM1-BD. The interactions of BIK1 with KAR9, BIM1, and KIP2 serve as positive controls (Carvalho et al 2004;Moore et al 2006;Wolyniak et al 2006).…”

Section: Resultsmentioning

confidence: 99%

The Spindle Positioning Protein Kar9p Interacts With the Sumoylation Machinery in Saccharomyces cerevisiae

et al. 2008

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Accurate positioning of the mitotic spindle is important for the genetic material to be distributed evenly in dividing cells, but little is known about the mechanisms that regulate this process. Here we report that two microtubule-associated proteins important for spindle positioning interact with several proteins in the sumoylation pathway. By two-hybrid analysis, Kar9p and Bim1p interact with the yeast SUMO Smt3p, the E2 enzyme Ubc9p, an E3 Nfi1p, as well as Wss1p, a weak suppressor of a temperature-sensitive smt3 allele. The physical interaction between Kar9p and Ubc9p was confirmed by in vitro binding assays. A singleamino-acid substitution in Kar9p, L304P disrupted its two-hybrid interaction with proteins in the sumoylation pathway, but retained its interactions with the spindle positioning proteins Bim1p, Stu2p, Bik1p, and Myo2p. The kar9-L304P mutant showed defects in positioning the mitotic spindle, with the spindle located more distally than normal. Whereas wild-type Kar9p-3GFP normally localizes to only the bud-directed spindle pole body (SPB), Kar9p-L304P-3GFP was mislocalized to both SPBs. Using a reconstitution assay, Kar9p was sumoylated in vitro. We propose a model in which sumoylation regulates spindle positioning by restricting Kar9p to one SPB. These findings raise the possibility that sumoylation could regulate other microtubule-dependent processes.

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Section: Resultsmentioning

confidence: 99%

The Spindle Positioning Protein Kar9p Interacts With the Sumoylation Machinery in Saccharomyces cerevisiae

et al. 2008

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“…Different pathways are known to be responsible for microtubule plus‐end accumulation of dynein. Kinesin‐dependent transport has been observed in fungi and neurons of metazoans, whereas EB1 family protein (EB)‐dependent end tracking has been described for non‐neuronal cultured mammalian cells (Carvalho et al , 2004; Moughamian et al , 2013; Roberts et al , 2014). …”

Section: Introductionmentioning

confidence: 99%

Combinatorial regulation of the balance between dynein microtubule end accumulation and initiation of directed motility

et al. 2017

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Cytoplasmic dynein is involved in a multitude of essential cellular functions. Dynein's activity is controlled by the combinatorial action of several regulatory proteins. The molecular mechanism of this regulation is still poorly understood. Using purified proteins, we reconstitute the regulation of the human dynein complex by three prominent regulators on dynamic microtubules in the presence of end binding proteins (EBs). We find that dynein can be in biochemically and functionally distinct pools: either tracking dynamic microtubule plus‐ends in an EB‐dependent manner or moving processively towards minus ends in an adaptor protein‐dependent manner. Whereas both dynein pools share the dynactin complex, they have opposite preferences for binding other regulators, either the adaptor protein Bicaudal‐D2 (BicD2) or the multifunctional regulator Lissencephaly‐1 (Lis1). BicD2 and Lis1 together control the overall efficiency of motility initiation. Remarkably, dynactin can bias motility initiation locally from microtubule plus ends by autonomous plus‐end recognition. This bias is further enhanced by EBs and Lis1. Our study provides insight into the mechanism of dynein regulation by dissecting the distinct functional contributions of the individual members of a dynein regulatory network.

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“…In both budding and fission yeast the CLIP-170 homologs, Bik1 and Tip1 respectively, also localize to the microtubule plus ends (Brunner and Nurse, 2000;Lin et al, 2001). However, in contrast to CLIP-170, Bik1 and Tip1 are transported to the plus end along the microtubule fiber by motor proteins, rather than binding to microtubule plus ends directly (Perez et al, 1999;Busch et al, 2004;Carvalho et al, 2004). CLIP-170 was shown to act as a positive regulator of microtubule growth in both yeast and humans (Berlin et al, 1990;Brunner and Nurse, 2000;Komarova et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

CLIP-170 facilitates the formation of kinetochore–microtubule attachments

Tanenbaum

Galjart

Vugt³

et al. 2005

EMBO J

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CLIP-170 is a microtubule 'plus end tracking' protein involved in several microtubule-dependent processes in interphase. At the onset of mitosis, CLIP-170 localizes to kinetochores, but at metaphase, it is no longer detectable at kinetochores. Although RNA interference (RNAi) experiments have suggested an essential role for CLIP-170 during mitosis, the molecular function of CLIP-170 in mitosis has not yet been revealed. Here, we used a combination of high-resolution microscopy and RNAi-mediated depletion to study the function of CLIP-170 in mitosis. We found that CLIP-170 dynamically localizes to the outer most part of unattached kinetochores and to the ends of growing microtubules. In addition, we provide evidence that a pool of CLIP-170 is transported along kinetochoremicrotubules by the dynein/dynactin complex. Interference with CLIP-170 expression results in defective chromosome congression and diminished kinetochoremicrotubule attachments, but does not detectibly affect microtubule dynamics or kinetochore-microtubule stability. Taken together, our results indicate that CLIP-170 facilitates the formation of kinetochore-microtubule attachments, possibly through direct capture of microtubules at the kinetochore.

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Cell Cycle Control of Kinesin-Mediated Transport of Bik1 (CLIP-170) Regulates Microtubule Stability and Dynein Activation

Cited by 213 publications

References 65 publications

The Spindle Positioning Protein Kar9p Interacts With the Sumoylation Machinery in Saccharomyces cerevisiae

The Spindle Positioning Protein Kar9p Interacts With the Sumoylation Machinery in Saccharomyces cerevisiae

Combinatorial regulation of the balance between dynein microtubule end accumulation and initiation of directed motility

CLIP-170 facilitates the formation of kinetochore–microtubule attachments

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