Diverse Roles of Cdc42 in Development and its Dysfunction in Developmental and Autoinflammatory Disorders
- By Cytoskeleton Inc. - Small G-Protein News
- Jan 28, 2025
Introduction
Cell division control protein 42 homolog (Cdc42), also known as cell division cycle 42, belongs to the Rho family of small GTPases and is notable as a central signaling hub that coordinates a myriad of fundamental cellular processes.1 Extensive studies have established key roles in regulating cytoskeletal dynamics and other downstream pathways to control cell shape and motility, differentiation, and cell cycle progression.2,3
Structurally, Cdc42 resembles other Rho GTPases and contains the two essential switch domains that mediate interactions with upstream regulators and downstream effectors, as well as enabling nucleotide binding.4 The protein is ubiquitously expressed2,5 and, in common with other Rho GTPases, relies on membrane localization to effect downstream signaling.2 This is achieved by posttranslational lipidation at Cys188, located in the C-terminal domain.1,6
Cdc42 is particularly known for its unique role in controlling cell polarity and in modulating polarized cell functions, including the proper formation of epithelial tight and adherens junctions.6-8 Thus, it is essential for correct morphogenesis of organs such as the heart, lungs, pancreas, and kidneys during early development.9,10 This newsletter summarizes the roles of Cdc42 in these processes and describes recently identified developmental and autoinflammatory disorders resulting from mutations in key functional domains.
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