Identification of novel nesprin-1 binding partners and cytoplasmic matrin-3 in processing bodies

TY - JOUR

T1 - Identification of novel nesprin-1 binding partners and cytoplasmic matrin-3 in processing bodies

AU - Rajgor, Dipen

AU - Hanley, Jonathan G.

AU - Shanahan, Catherine M.

PY - 2016/10/12

Y1 - 2016/10/12

N2 - Nesprins are highly conserved spectrin repeat-containing scaffold proteins predominantly known to function at the nuclear envelope (NE). However, nesprin isoforms are emerging with localizations and scaffolding functions at sites away from the NE, suggesting their functions are more diverse than originally thought. In this study, we combined nesprin-1 coimmunoprecipitations with mass spectrometry to identify novel nesprin-1 binding partners for isoforms that localize to subcellular compartments beyond the NE. We show that one of these interactors, matrin-3 (matr3), localizes to mRNA processing bodies (PBs), where we have previously shown a nesprin-1 isoform to localize. Furthermore, we show that Matr3 is part of PB mRNP complexes, is a regulator of miRNA-mediated gene silencing, and possibly shuttles to stress granules in stressed cells. More importantly, we identify a new C-terminally truncated Matr3 isoform that is likely to be involved in these functions and PB localization. This study highlights several novel nesprin-1 binding partners and a new function and localization for Matr3 in cytoplasmic RNA granules.

AB - Nesprins are highly conserved spectrin repeat-containing scaffold proteins predominantly known to function at the nuclear envelope (NE). However, nesprin isoforms are emerging with localizations and scaffolding functions at sites away from the NE, suggesting their functions are more diverse than originally thought. In this study, we combined nesprin-1 coimmunoprecipitations with mass spectrometry to identify novel nesprin-1 binding partners for isoforms that localize to subcellular compartments beyond the NE. We show that one of these interactors, matrin-3 (matr3), localizes to mRNA processing bodies (PBs), where we have previously shown a nesprin-1 isoform to localize. Furthermore, we show that Matr3 is part of PB mRNP complexes, is a regulator of miRNA-mediated gene silencing, and possibly shuttles to stress granules in stressed cells. More importantly, we identify a new C-terminally truncated Matr3 isoform that is likely to be involved in these functions and PB localization. This study highlights several novel nesprin-1 binding partners and a new function and localization for Matr3 in cytoplasmic RNA granules.

UR - http://www.scopus.com/inward/record.url?scp=85001930703&partnerID=8YFLogxK

U2 - 10.1091/mbc.E16-06-0346

DO - 10.1091/mbc.E16-06-0346

M3 - Article

AN - SCOPUS:85001930703

SN - 1059-1524

VL - 27

SP - 3894

EP - 3902

JO - Molecular biology of the cell

JF - Molecular biology of the cell

IS - 24

ER -