NCBI Summary:
This gene encodes a member of the RAB family, which belongs to the small GTPase superfamily. GTPases of the RAB family bind to various effectors to regulate the targeting and fusion of transport carriers to acceptor compartments. This protein is located at the Golgi apparatus, which regulates trafficking in both a retrograde (from early endosomes and Golgi to the endoplasmic reticulum) and an anterograde (from the Golgi to the plasma membrane) directions. Myosin II is an effector of this protein in these processes. This protein is also involved in assembly of human cytomegalovirus (HCMV) by interacting with the cellular protein Bicaudal D1, which interacts with the HCMV virion tegument protein, pp150. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
General function
Enzyme
Comment
Cellular localization
Golgi
Comment
Ovarian function
Oogenesis, Oocyte maturation, Early embryo development
Comment
Involvement of Rab6a in organelle rearrangement and cytoskeletal organization during mouse oocyte maturation. Ma R et al. (2016) Rab GTPases have been reported to define the identity and transport routes of vesicles. Rab6 is one of the most extensively studied Rab proteins involved in regulating organelle trafficking and integrity maintenance. However, to date, the function of Rab6 in mammalian oocytes has not been addressed. Here we report severe disorganization of endoplasmic reticulum upon specific knockdown of Rab6a in mouse oocytes. In line with this finding, intracellular Ca(2+) stores are accordingly reduced in Rab6a-depleted oocytes. Furthermore, in these oocytes, we observe the absence of cortical granule free domain, which is a kind of special organelle in matured oocytes and its exocytosis is calcium dependent. On the other hand, following Rab6a knockdown, the prominent defects of cytoskeletal structures are detected during oocyte meiosis. In particular, the majority of Rab6a-depleted oocytes fail to form the actin cap, and the frequency of spindle defects and chromosome misalignment is significantly elevated. In summary, our data reveal that Rab6a not only participates in modulating the organization of oocyte organelles, but also is a novel regulator of meiotic apparatus in mammalian oocytes.//////////////////
Rab6a is a novel regulator of meiotic apparatus and maturational progression in mouse oocytes. Hou X et al. (2016) Rab family GTPases have been well known to regulate intracellular vesicle transport, however their function in mammalian oocytes has not been addressed. In this study, we report that when Rab6a is specifically knockdown, mouse oocytes are unable to progress normally through meiosis, arresting at metaphase I. Moreover, in these oocytes, the defects of chromosome alignment and spindle organization are readily observed during maturation, and resultantly increasing the aneuploidy incidence. We further reveal that kinetochore-microtubule attachments are severely compromised in Rab6a-depleted oocytes, which may in part mediate the meiotic phenotypes described above. In addition, when Rab6a function is altered, BubR1 levels on the kinetochores are markedly increased in metaphase oocytes, indicating the activation of spindle assembly checkpoint. In sum, we identify Rab6a as an important player in modulating oocyte meiosis, specifically the chromosome/spindle organization and metaphase-anaphase transition.//////////////////
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Rab6 is required for the exocytosis of cortical granules and the recruitment of separase to the granules during the oocyte-to-embryo transition in Caenorhabditis elegans. Kimura K et al. Remodeling of the embryo surface after fertilization is mediated by the exocytosis of cortical granules derived from the Golgi complex. This process is essential for oocyte-to-embryo transition in many species. However, how the fertilization signal reaches the cortical granules for their timely exocytosis is largely unknown. In Caenorhabditis elegans, the recruitment of separase, a downstream effector of the fertilization signal, to the cortical granules is essential for exocytosis because separase is required for membrane fusion. However, the molecule that recruits separase to the cortical granules remains unidentified. In this study, we found that Rab6, a Golgi-associated GTPase, is essential to recruit separase to the cortical granules in C. elegans embryos. Knockdown of the rab-6.1 gene, a Rab6 homologue in C. elegans, resulted in failure of the membrane fusion step of cortical granule exocytosis. Using a transgenic strain that expresses GFP-fused RAB-6.1, we found that RAB-6.1 temporarily co-localized with separase on the cortical granules for a few minutes and then was dispersed in the cytoplasm concomitantly with membrane fusion. We found that RAB-6.1 as well as cyclin-dependent kinase (CDK)-1 and anaphase promoting complex/cyclosome (APC/C) was required to recruit separase to the cortical granules. RAB-6.1 was not required for the chromosome segregation process, unlike CDK-1, APC/C, and SEP-1. The results indicate that RAB-6.1 is required specifically for the membrane fusion step of exocytosis and for the recruitment of separase to the granules. Thus, RAB-6.1 is an important molecule for the timely exocytosis of the cortical granules during oocyte-to-embryo transition.