Dendritic cells (DCs) have essential roles in early detection of pathogens and activation of both innate and adaptive immune responses. Whereas human DCs are resistant to productive HIV-1 replication, they have a unique ability to take up virus and transmit it efficiently to T lymphocytes. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. While performing an shRNA screen in human primary monocyte-derived DCs, to gain insights into this cell biological process, we discovered the role played by tetraspanin-7 (TSPAN7). This member of the tetraspanin family appears to be a positive regulator of actin nucleation and stabilization, through the ARP2/3 complex. By doing so, TSPAN7 limits HIV-1 endocytosis and maintains viral particles on actin-rich dendrites for an efficient transfer toward T lymphocytes. While studying the function of TSPAN7 in the control of actin nucleation, we also discovered the existence in DCs of two opposing forces at the plasma membrane: actin nucleation, a protrusive force which seems to counterbalance actomyosin contraction.
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Cover Image
Cover Image
An artistic model of the ‘molecular scissor’ ADAM10 (displayed in orange) at the cell surface, shown cleaving one of its substrates (green). ADAM10 is regulated by one of six TspanC8 tetraspanins (displayed in white or blue). The TspanC8s have distinct mechanisms of binding to ADAM10 and appear to dictate its substrate specificity. For more information, please see pages 719–730 in this issue of the Biochemical Society Transactions. Designer: Justyna Szyroka Artist: Eduardo Oliveira - Graphics Designer and Animator. Image kindly provided by Michael G Tomlinson.
TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells
Mickaël M. Ménager; TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells. Biochem Soc Trans 15 June 2017; 45 (3): 703–708. doi: https://doi.org/10.1042/BST20160439
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