Tulp3 Regulates Renal Cystogenesis by Trafficking of Cystoproteins to Cilia

Current Biology : CB
Sun-Hee HwangSaikat Mukhopadhyay

Abstract

Polycystic kidney disease proteins, polycystin-1 and polycystin-2, localize to primary cilia. Polycystin knockouts have severe cystogenesis compared to ciliary disruption, whereas simultaneous ciliary loss suppresses excessive cyst growth. These data suggest the presence of a cystogenic activator that is inhibited by polycystins and an independent but relatively minor cystogenic inhibitor, either of which are cilia dependent. However, current genetic models targeting cilia completely ablate the compartment, making it difficult to uncouple cystoprotein function from ciliary localization. Thus, the role of cilium-generated signaling in cystogenesis is unclear. We recently demonstrated that the tubby family protein Tulp3 determines ciliary trafficking of polycystins in kidney collecting duct cells without affecting protein levels or cilia. Here, we demonstrate that embryonic-stage, nephron-specific Tulp3 knockout mice developed cystic kidneys, while retaining intact cilia. Cystic kidneys showed increased mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), mTOR, and persistently high cyclic AMP (cAMP) signaling, suggesting contribution of multiple factors to cystogenesis. Based on kidney-to-body-wei...Continue Reading

Citations

May 3, 2020·Proceedings of the National Academy of Sciences of the United States of America·Woongsu HanChul Hoon Kim
Jun 2, 2020·Seminars in Cell & Developmental Biology·Ming Ma
Nov 15, 2020·The Journal of Biological Chemistry·Evan M KerekBasil P Hubbard
Feb 19, 2021·Biochemical Society Transactions·Pablo Barbeito, Francesc R Garcia-Gonzalo
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Wei WangPamela V Tran

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