Cdc42 is a Ras-related GTP-binding protein that has been implicated in the regulation of the actin cytoskeleton and cell morphology. IQGAP is a protein of molecular mass ~180 kDa from rabbit liver cytosol (designated p180), which binds preferentially to the GTP- and guanosine 5 -3-O-(thio)triphosphate-bound forms of Cdc42. Binding of p180 to GTP-bound Cdc42 maintains it in the GTP-bound state. The IQGAP1 cDNA encodes a 1,657-amino acid polypeptide with significant similarity to the Ras-related GTPase-activating (RasGAP) family of proteins (see OMIM 139150). The N-terminal domain contains 6 copies of a unique motif and 4 IQ motifs (named for the presence of tandem isoleucine and glutamine residues), which are known to modulate binding with calmodulin
General function
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Cellular localization
Plasma membrane
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Ovarian function
Oocyte maturation
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Cdc42 protein acts upstream of IQGAP1 and regulates cytokinesis in mouse oocytes and embryos. Bielak-Zmijewska A et al. Cdc42 and Rac1 Rho family GTPases, and their interacting protein IQGAP1 are the key regulators of cell polarity. We examined the role of Cdc42 and IQGAP1 in establishing the polarity of mouse oocyte and regulation of meiotic and mitotic divisions. We showed that Cdc42 was localized on the microtubules of meiotic and mitotic spindle and in the cortex of mouse oocyte and cleaving embryos. The IQGAP1 was present in the cytoplasm and cortex of growing and fully-grown oocytes. During maturation it disappeared from the cortex and during meiotic and mitotic cytokinesis it concentrated in the contractile ring. Toxin B inhibition of the binding activity of Cdc42 changed the localization of IQGAP1, inhibited emission of the first polar body, and caused disappearance of the cortical actin without affecting the migration of meiotic spindle. This indicates, that in maturing oocytes accumulation of cortical actin is not indispensable for spindle migration. In zygotes treated with toxin B actin cytoskeleton was rearranged and the first and/or subsequent cytokinesis were inhibited. Our results indicate that Cdc42 acts upstream of IQGAP1 and is involved in regulation of cytokinesis in mouse oocytes and cleaving embryos, rather than in establishing the polarity of the oocyte.
Expression regulated by
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Ovarian localization
Oocyte
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Robert A. Taft et al 2002 reported the identification of Genes Encoding Mouse Oocyte Secretory and Transmembrane Proteins by a Signal Sequence Trap.
. At all stages of follicular development, oocytes interact with surrounding granulosa cells and promote their differentiation into the types of cells that support further oocyte growth and developmental competence. These interactions suggest the existence of an oocyte-granulosa cell regulatory loop that includes both secreted proteins and cell surface receptors on both cell types. Factors involved in the regulatory loop will therefore contain a signal sequence, which can be used to identify them through a signal sequence trap (SST). A screen of an oocyte SST library identified three classes of oocyte-expressed sequences: known mouse genes, sequences homologous to known mammalian genes, and novel sequences of unknown function. Many of the recovered genes may have roles in the oocyte-granulosa cell regulatory loop. For several of the known mouse genes, new roles in follicular development are implied by identification of their expression, for the first time, in the oocyte. The future characterization of novel sequences may lead to the identification of novel proteins participating in the regulatory loop.
IQGAP is one of the oocyte genes identified by the SST approach. It is expressed by oocytes of preantral and antral follicles and by their companion granulosa cells.