Narayana, Y.V. and Gadgil, C. and Mote, R.D. and Rajan, R. and Subramanyam, D. (2019) Clathrin-MediatedEndocytosis Regulates a Balance between Opposing Signals to Maintain thePluripotent State of Embryonic Stem Cells. Stem Cell Reports. , 12 (1). pp. 152-164.

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Abstract

Endocytosis is implicated in the maintenance of embryonic stem cell (ESC) pluripotency, although its exact role and the identity ofmolecular players remain poorly understood. Here, we show that the clathrin heavy chain (CLTC), involved in clathrin-mediatedendocytosis (CME), is vital for maintaining mouse ESC (mESC) pluripotency. Knockdown ofCltcresulted in a loss of pluripotency accom-panied by reduced E-cadherin (E-CAD) levels and increased levels of transforming growth factorb(TGF-b) and extracellular signal-regu-lated kinase (ERK) signaling. We demonstrate that both E-CAD and TGF-breceptor type 1 (TGF-bR1) are internalized through CME inmESCs. While E-CAD is recycled, TGF-bR1 is targeted for lysosomal degradation thus maintaining inverse levels of these molecules.Finally, we show that E-CAD interacts with ERK, and that the decreased pluripotency upon CME loss can be rescued by inhibitingTGF-bR, MEK, and GSK3b, or overexpressing E-CAD. Our results demonstrate that CME is critical for balancing signaling outputs toregulate ESC pluripotency, and possibly cell fate choices in early development.

Item Type:	Article
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	13 Feb 2020 06:38
Last Modified:	13 Feb 2020 06:42
URI:	http://nccs.sciencecentral.in/id/eprint/631

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