Donta Maxsam S, Srivastava Yogesh, McCrea Pierre D
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Program in Genetics and Epigenetics, The University of Texas MD Anderson Cancer Center University of Texas Health Science Center Houston Graduate School of Biomedical Science, Houston, TX, United States.
Front Cell Neurosci. 2022 Jul 4;16:939143. doi: 10.3389/fncel.2022.939143. eCollection 2022.
Small Rho GTPases are molecular switches that are involved in multiple processes including regulation of the actin cytoskeleton. These GTPases are activated (turned on) and inactivated (turned off) through various upstream effector molecules to carry out many cellular functions. One such upstream modulator of small Rho GTPase activity is delta-catenin, which is a protein in the p120-catenin subfamily that is enriched in the central nervous system. Delta-catenin affects small GTPase activity to assist in the developmental formation of dendrites and dendritic spines and to maintain them once they mature. As the dendritic arbor and spine density are crucial for synapse formation and plasticity, delta-catenin's ability to modulate small Rho GTPases is necessary for proper learning and memory. Accordingly, the misregulation of delta-catenin and small Rho GTPases has been implicated in several neurological and non-neurological pathologies. While links between delta-catenin and small Rho GTPases have yet to be studied in many contexts, known associations include some cancers, Alzheimer's disease (AD), Cri-du-chat syndrome, and autism spectrum disorder (ASD). Drawing from established studies and recent discoveries, this review explores how delta-catenin modulates small Rho GTPase activity. Future studies will likely elucidate how PDZ proteins that bind delta-catenin further influence small Rho GTPases, how delta-catenin may affect small GTPase activity at adherens junctions when bound to N-cadherin, mechanisms behind delta-catenin's ability to modulate Rac1 and Cdc42, and delta-catenin's ability to modulate small Rho GTPases in the context of diseases, such as cancer and AD.
小Rho GTP酶是分子开关，参与包括肌动蛋白细胞骨架调节在内的多种过程。这些GTP酶通过各种上游效应分子被激活（开启）和失活（关闭），以执行许多细胞功能。小Rho GTP酶活性的一种上游调节剂是δ-连环蛋白，它是p120-连环蛋白亚家族中的一种蛋白质，在中枢神经系统中含量丰富。δ-连环蛋白影响小GTP酶活性，以协助树突和树突棘的发育形成，并在它们成熟后维持其状态。由于树突分支和棘密度对于突触形成和可塑性至关重要，δ-连环蛋白调节小Rho GTP酶的能力对于正常的学习和记忆是必要的。因此，δ-连环蛋白和小Rho GTP酶的失调与多种神经和非神经病理学有关。虽然在许多情况下，δ-连环蛋白和小Rho GTP酶之间的联系尚未得到研究，但已知的关联包括一些癌症、阿尔茨海默病（AD）、猫叫综合征和自闭症谱系障碍（ASD）。基于已有的研究和最近的发现，本综述探讨了δ-连环蛋白如何调节小Rho GTP酶活性。未来的研究可能会阐明与δ-连环蛋白结合的PDZ蛋白如何进一步影响小Rho GTP酶，δ-连环蛋白与N-钙黏蛋白结合时如何在黏附连接处影响小GTP酶活性，δ-连环蛋白调节Rac1和Cdc42能力背后的机制，以及δ-连环蛋白在癌症和AD等疾病背景下调节小Rho GTP酶的能力。
