Microtubule segment stabilization by RASSF1A is required for proper microtubule dynamics and Golgi integrity.
The tumor suppressor and microtubule-associated protein Ras association domain family 1A (RASSF1A) has a major effect on many cellular processes, such as cell cycle progression and apoptosis. RASSF1A expression is frequently silenced in cancer and is associated with increased metastasis. Therefore we tested the hypothesis that RASSF1A regulates microtubule organization and dynamics in interphase cells, as well as its effect on Golgi integrity and cell polarity. Our results show that RASSF1A uses a unique microtubule-binding pattern to promote site-specific microtubule rescues, and loss of RASSF1A leads to decreased microtubule stability. Furthermore, RASSF1A-associated stable microtubule segments are necessary to prevent Golgi fragmentation and dispersal in cancer cells and maintain a polarized cell front. These results indicate that RASSF1A is a key regulator in the fine tuning of microtubule dynamics in interphase cells and proper Golgi organization and cell polarity.
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 JG Brown Cancer Center, University of Louisville, Louisville, KY 40202.
Christopher
C
Arnette
Nadia
N
Efimova
Xiaodong
X
Zhu
Geoffrey J
GJ
Clark
Irina
I
Kaverina
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002455:Cell Division; D002461:Cell Line, Transformed; D016764:Cell Polarity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D015870:Gene Expression; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D015739:Nocodazole / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059008:Time-Lapse Imaging; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
C411762:RASSF1 protein, human; D034741:RNA, Small Interfering; D014404:Tubulin; D050257:Tubulin Modulators; D025521:Tumor Suppressor Proteins; D015739:Nocodazole