The growth determinants and transport properties of tunneling nanotube networks between B lymphocytes

Autor: Miklós S.Z. Kellermayer, Tamás Bozó, Ádám Oszvald, Emese Izsépi, Miklós Nyitrai, Beáta Biri, Anikó Osteikoetxea-Molnár, Péter Németh, László Nyitray, Mariann Kremlitzka, János Matkó, Edina Szabó-Meleg, Eszter Angéla Tóth
Rok vydání: 2016
Předmět:
Zdroj: Cellular and Molecular Life Sciences. 73:4531-4545
ISSN: 1420-9071
1420-682X
DOI: 10.1007/s00018-016-2233-y
Popis: Tunneling nanotubes (TNTs) are long intercellular connecting structures providing a special transport route between two neighboring cells. To date TNTs have been reported in different cell types including immune cells such as T-, NK, dendritic cells, or macrophages. Here we report that mature, but not immature, B cells spontaneously form extensive TNT networks under conditions resembling the physiological environment. Live-cell fluorescence, structured illumination, and atomic force microscopic imaging provide new insights into the structure and dynamics of B cell TNTs. Importantly, the selective interaction of cell surface integrins with fibronectin or laminin extracellular matrix proteins proved to be essential for initiating TNT growth in B cells. These TNTs display diversity in length and thickness and contain not only F-actin, but their majority also contain microtubules, which were found, however, not essential for TNT formation. Furthermore, we demonstrate that Ca2+-dependent cortical actin dynamics exert a fundamental control over TNT growth-retraction equilibrium, suggesting that actin filaments form the TNT skeleton. Non-muscle myosin 2 motor activity was shown to provide a negative control limiting the uncontrolled outgrowth of membranous protrusions. Moreover, we also show that spontaneous growth of TNTs is either reduced or increased by B cell receptor- or LPS-mediated activation signals, respectively, thus supporting the critical role of cytoplasmic Ca2+ in regulation of TNT formation. Finally, we observed transport of various GM1/GM3+ vesicles, lysosomes, and mitochondria inside TNTs, as well as intercellular exchange of MHC-II and B7-2 (CD86) molecules which may represent novel pathways of intercellular communication and immunoregulation.
Databáze: OpenAIRE
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