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FASEB J. 2019 May 21:fj201900136R. doi: 10.1096/fj.201900136R. [Epub ahead of print]

EB1- and EB2-dependent anterograde trafficking of TRPM4 regulates focal adhesion turnover and cell invasion.

Author information

1
Program of Cellular and Molecular Biology and.
2
Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD), Santiago, Chile.
3
Program of Physiology and Biophysics, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
4
Multidisciplinary Scientific Nucleus and.
5
Center for Bioinformatics and Molecular Simulation, Universidad de Talca, Talca, Chile.
6
Department of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago, Chile; and.
7
The Wound Repair, Treatment, and Health (WoRTH) Initiative, Santiago, Chile.

Abstract

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated nonselective cationic channel involved in a wide variety of physiologic and pathophysiological processes. Bioinformatics analyses of the primary sequence of TRPM4 allowed us to identify a putative motif for interaction with end-binding (EB) proteins, which are microtubule plus-end tracking proteins. Here, we provide novel data suggesting that TRPM4 interacts with EB proteins. We show that mutations of the putative EB binding motif abolish the TRPM4-EB interaction, leading to a reduced expression of the mature population of the plasma membrane channel and instead display an endoplasmic reticulum-associated distribution. Furthermore, we demonstrate that EB1 and EB2 proteins are required for TRPM4 trafficking and functional activity. Finally, we demonstrated that the expression of a soluble fragment containing the EB binding motif of TRPM4 reduces the plasma membrane expression of the channel and affects TRPM4-dependent focal adhesion disassembly and cell invasion processes.-Blanco, C., Morales, D., Mogollones, I., Vergara-Jaque, A., Vargas, C., Álvarez, A., Riquelme, D., Leiva-Salcedo, E., González, W., Morales, D., Maureira, D., Aldunate, I., Cáceres, M., Varela, D., Cerda, O. EB1- and EB2-dependent anterograde trafficking of TRPM4 regulates focal adhesion turnover and cell invasion.

KEYWORDS:

EB proteins; ER export; TRP channels

PMID:
31112396
DOI:
10.1096/fj.201900136R

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