TY - JOUR
T1 - M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
AU - Hase, Koji
AU - Kimura, Shunsuke
AU - Takatsu, Hiroyuki
AU - Ohmae, Masumi
AU - Kawano, Sayaka
AU - Kitamura, Hiroshi
AU - Ito, Masatoshi
AU - Watarai, Hiroshi
AU - Hazelett, C. Clayton
AU - Yeaman, Charles
AU - Ohno, Hiroshi
N1 - Funding Information:
We would like to thank I. Yamashita and Y. Fujimura for technical assistance, and. P. Burrows and C. Blaumueller for critically reviewing the manuscript. This study was supported in part by Grants-in-Aid for Young Scientists (B) (K.H.), Scientific Research (B) (H.O.), Scientific Research in Priority Areas (H.O. and K.H.) and Scientific Research on Innovative Areas (H.O.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and grants from the National Institutes of Health (GM067002; C.Y.) and the Takeda Science Foundation (K.H.).
PY - 2009/12
Y1 - 2009/12
N2 - Cell-cell communication is essential for the development and homeostasis of multicellular organisms. Recently, a new type of cell-cell communication was discovered that is based on the formation of thin membranous nanotubes between remote cells. These long membrane tethers, termed tunneling nanotubes (TNTs), form an intercellular conduit and have been shown to enable the transport of various cellular components and signals. However, the molecular basis for TNT formation remains to be elucidated. Here we report that a mammalian protein, M-Sec, induces de novo formation of numerous membrane protrusions extending from the plasma membrane, some of which tether onto adjacent cells and subsequently form TNT-like structures. Depletion of M-Sec by RNA interference (RNAi) greatly reduced endogenous TNT formation as well as intercellular propagation of a calcium flux in a macrophage cell line. Furthermore, blockage of the interaction of M-Sec with Ral and the exocyst complex, which serves as a downstream effector of Ral, attenuated the formation of membrane nanotubes. Our results reveal that M-Sec functions as a key regulator of membrane nanotube formation through interaction with the Ral-exocyst pathway.
AB - Cell-cell communication is essential for the development and homeostasis of multicellular organisms. Recently, a new type of cell-cell communication was discovered that is based on the formation of thin membranous nanotubes between remote cells. These long membrane tethers, termed tunneling nanotubes (TNTs), form an intercellular conduit and have been shown to enable the transport of various cellular components and signals. However, the molecular basis for TNT formation remains to be elucidated. Here we report that a mammalian protein, M-Sec, induces de novo formation of numerous membrane protrusions extending from the plasma membrane, some of which tether onto adjacent cells and subsequently form TNT-like structures. Depletion of M-Sec by RNA interference (RNAi) greatly reduced endogenous TNT formation as well as intercellular propagation of a calcium flux in a macrophage cell line. Furthermore, blockage of the interaction of M-Sec with Ral and the exocyst complex, which serves as a downstream effector of Ral, attenuated the formation of membrane nanotubes. Our results reveal that M-Sec functions as a key regulator of membrane nanotube formation through interaction with the Ral-exocyst pathway.
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U2 - 10.1038/ncb1990
DO - 10.1038/ncb1990
M3 - Article
C2 - 19935652
AN - SCOPUS:73349111312
VL - 11
SP - 1427
EP - 1432
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 12
ER -