Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation.
CLIPs are microtubule plus end-associated proteins that mediate interactions required for cell polarity and cell division. Here we demonstrate that budding yeast Bik1, unlike its human ortholog CLIP-170, is targeted to the microtubule plus end by a kinesin-dependent transport mechanism. Bik1 forms a complex with the kinesin Kip2. Fluorescently labeled Bik1 and Kip2 comigrate along individual microtubules. Bik1 exists in distinct intracellular pools: a stable pool at the spindle pole body that is depleted during cell cycle progression, a soluble pool from which Bik1 can be recruited during microtubule initiation, and a dynamic plus end pool maintained by Kip2. Kip2 stabilizes microtubules by targeting Bik1 to the plus end and Kip2 levels are controlled during the cell cycle. As with Bik1, the targeting of dynein to the microtubule plus end requires Kip2. These findings reveal a central role for Kip2-dependent transport in the cell cycle control of microtubule dynamics and dynein-dependent motility.
Carvalho
Pedro
P
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
Gupta
Mohan L
ML
Hoyt
M Andrew
MA
Pellman
David
D
D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D004398:Dyneins / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D020409:Molecular Motor Proteins; D009363:Neoplasm Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
C488173:Bik1 protein, S cerevisiae; C075341:KIP2 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; C076744:cytoplasmic linker protein 170; D004398:Dyneins; D016547:Kinesins