Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

TY - JOUR

T1 - Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

AU - Elias, Bertha C

AU - Das, Amrita

AU - Parekh, Diptiben V

AU - Mernaugh, Glenda

AU - Adams, Rebecca

AU - Yang, Zhufeng

AU - Brakebusch, Cord

AU - Pozzi, Ambra

AU - Marciano, Denise K

AU - Carroll, Thomas J

AU - Zent, Roy

N1 - © 2015. Published by The Company of Biologists Ltd.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and maintenance, its exact molecular function in kidney development is not well understood. In this study, we define the specific role of Cdc42 during murine kidney epithelial tubulogenesis by deleting it selectively at the initiation of ureteric bud or metanephric mesenchyme development. Deletion in either lineage results in abnormal tubulogenesis, with profound defects in polarity, lumen formation and the actin cytoskeleton. Ultimately, these defects lead to renal failure. Additionally, in vitro analysis of Cdc42-null collecting duct cells shows that Cdc42 controls these processes by regulating the polarity Par complex (Par3-Par6-aPKC-Cdc42) and the cytoskeletal proteins N-Wasp and ezrin. Thus, we conclude that the principal role of Cdc42 in ureteric bud and metanephric mesenchyme development is to regulate epithelial cell polarity and the actin cytoskeleton.

AB - The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and maintenance, its exact molecular function in kidney development is not well understood. In this study, we define the specific role of Cdc42 during murine kidney epithelial tubulogenesis by deleting it selectively at the initiation of ureteric bud or metanephric mesenchyme development. Deletion in either lineage results in abnormal tubulogenesis, with profound defects in polarity, lumen formation and the actin cytoskeleton. Ultimately, these defects lead to renal failure. Additionally, in vitro analysis of Cdc42-null collecting duct cells shows that Cdc42 controls these processes by regulating the polarity Par complex (Par3-Par6-aPKC-Cdc42) and the cytoskeletal proteins N-Wasp and ezrin. Thus, we conclude that the principal role of Cdc42 in ureteric bud and metanephric mesenchyme development is to regulate epithelial cell polarity and the actin cytoskeleton.

KW - Animals

KW - Cell Polarity

KW - Cytoskeleton

KW - Epithelial Cells

KW - Kidney Tubules

KW - Mice

KW - cdc42 GTP-Binding Protein

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1242/jcs.164509

DO - 10.1242/jcs.164509

M3 - Journal article

C2 - 26490995

SN - 0021-9533

VL - 128

SP - 4293

EP - 4305

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 23

ER -