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EB1‐ and EB2‐dependent anterograde trafficking of TRPM4 regulates focal adhesion turnover and cell invasion
Author(s) -
Blanco Constanza,
Morales Danna,
Mogollones Ignacio,
VergaraJaque Ariela,
Vargas Carla,
Álvarez Alhejandra,
Riquelme Denise,
LeivaSalcedo Elías,
González Wendy,
Morales Diego,
Maureira Diego,
Aldunate Ismael,
Cáceres Mónica,
Varela Diego,
Cerda Oscar
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900136r
Subject(s) - microbiology and biotechnology , endoplasmic reticulum , focal adhesion , cell adhesion , chemistry , plasma protein binding , hek 293 cells , cell migration , cell membrane , membrane protein , cell , biology , receptor , biochemistry , membrane , signal transduction
Transient receptor potential melastatin 4 (TRPM4) is a Ca 2+ ‐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. FASEB J. 33, 9434–9452 (2019). www.fasebj.org