High impact information on Cdc42

• Normal patterns of R cell connectivity require Pak's kinase activity and binding sites for both Dock and Cdc42/Rac [1].
• In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline [2].
• Dendrite development is altered in prospero mutants and in transgenic embryos expressing a constitutively active form of the small GTPase cdc42 [3].
• Dorsal closure can also be blocked by dominant negative Drosophila cdc42, which has been shown to act upstream of JNKK in vertebrates [4].
• Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis [5].

Biological context of Cdc42

• We propose a role for Mbt as a downstream effector of Cdc42 in photoreceptor cell morphogenesis [6].
• Unlike Ral and Cdc42, which are ubiquitously expressed, GEFmeso exerts distinct spatio-temporal expression patterns during embryonic development, suggesting a tissue-restricted function of the GEF in vivo [7].
• We find that Cdc42(-) epithelial cells fail to elongate into a columnar cell shape and cannot maintain a monolayered epithelial structure [8].
• In contrast to previous studies, we find no requirement for Cdc42 in cell division or in activation of the Jun N-terminal kinase pathway [8].
• In addition, Cdc42 function is not required for cytoplasmic actin filament assembly in the nurse cells during oogenesis, although it may facilitate this process [8].

Anatomical context of Cdc42

• Besides regulation of kinase activity, another important function of Cdc42 is to recruit Mbt to adherens junctions [6].
• We found that RhoA and Rac1 have distinct roles in peripheral glial cell migration and nerve ensheathement; however, Cdc42 does not have a significant role in peripheral glial development [9].
• Cdc42 appears not to be required within macrophages but in other tissues of the embryo to guide macrophages to the ventral trunk region [10].
• Microinjection of constitutively active Cdc42 (V12Cdc42) disrupts the actomyosin cytoskeleton during cellularization (Crawford et al., Dev. Biol., 204, 151-164 (1998)) [11].
• A hair begins as a single membrane outgrowth from each wing epithelial cell, and its distal orientation is determined by the restriction of outgrowth to a single distal site on the cell circumference (Wong, L., and P. Adler. 1993. J. Cell Biol. 123:209-211.). We have examined the roles of Cdc42 and Rac1 in the formation of wing hairs [12].

Associations of Cdc42 with chemical compounds

• We have characterized Drosophila melanogaster ACK (DACK), one of two members of the ACK family of nonreceptor tyrosine kinases in DROSOPHILA: The ACKs are likely effectors for the small GTPase Cdc42, but signaling by these proteins remains poorly defined [13].
• Of the 10 agents microinjected, C3 exoenzyme, constitutively active Cdc42, and dominant negative Rho have a specific and indistinguishable effect: the actomyosin cytoskeleton is disrupted, cellularization halts, and embryogenesis arrests [14].
• Down regulation of the leading edge cytoskeleton may be controlled by the serine/threonine kinase DPAK, a potential Drac1/Dcdc42 effector [15].
• In contrast, we find that association with the key signaling molecules CDC42 and PIP2 is not an essential requirement, implying that activation of Wsp function in vivo depends on additional or alternative signaling pathways [16].

Physical interactions of Cdc42

• Similarly, in yeast, RotundRacGAP interacts specifically with Drac1 and Dcdc42, as well as with their activated V12 forms, showing a particularly strong interaction with Dcdc42V12 [17].

Regulatory relationships of Cdc42

• Apical localization of Par-6 requires its interaction with activated Cdc42 and dominant-active or dominant-negative Cdc42 disrupt epithelial polarity, suggesting that activation of this GTPase is crucial for the establishment of epithelial polarity [18].
• We conclude that Cdc42 regulates aPKC localization and activity downstream of Bazooka, thereby directing neuroblast cell polarity and asymmetric cell division [19].

Other interactions of Cdc42

• Cdc42 and Rac1 are members of the rho family of small guanosinetriphosphatases and are required for a diverse set of cytoskeleton-membrane interactions in different cell types [20].
• Drosophila RhoGAP68F is similar to the mammalian protein p50RhoGAP/Cdc42GAP, which exhibits strong GAP activity toward Cdc42 [21].
• Mbt, a Drosophila PAK protein, combines with Cdc42 to regulate photoreceptor cell morphogenesis [6].
• In addition, p21-binding domain pull-down assays demonstrate that DRhoGEF4 activates RhoA, but neither Rac1 nor Cdc42 in HEK293 cells [22].
• Cdc42 binds to a CRIB domain adjacent to the PDZ domain, increasing the affinity of the Par-6 PDZ for its carboxy-terminal ligand by approximately 13-fold [23].

References