M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex.
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.
Hase
Koji
K
Laboratory for Epithelial Immunobiology, Kanagawa 230-0045, Japan.
Kimura
Shunsuke
S
Takatsu
Hiroyuki
H
Ohmae
Masumi
M
Kawano
Sayaka
S
Kitamura
Hiroshi
H
Ito
Masatoshi
M
Watarai
Hiroshi
H
Hazelett
C Clayton
CC
Yeaman
Charles
C
Ohno
Hiroshi
H
D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis; D006801:Humans; D051379:Mice; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C511409:Exoc2 protein, mouse; C545682:M-sec protein, mouse; D034741:RNA, Small Interfering; D048069:Tumor Necrosis Factors; D033921:Vesicular Transport Proteins; C118120:Rala protein, mouse; D020725:ral GTP-Binding Proteins