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Small GTPases. 2018 Jul 4;9(4):349-351. doi: 10.1080/21541248.2016.1235004. Epub 2016 Nov 1.

Rab3a and Rab10 are regulators of lysosome exocytosis and plasma membrane repair.

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a CEDOC, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa , Lisboa , Portugal.


Disruption of the cell plasma membrane can occur due to mechanical damage, pore forming toxins, etc. Resealing or plasma membrane repair (PMR) is the emergency response required for cell survival. It is triggered by Ca2+ entering through the disruption, causing organelles such as lysosomes located underneath the plasma membrane to fuse rapidly with the adjacent plasma membrane. We have recently identified some of the molecular traffic machinery that is involved in this vital process. Specifically, we showed that 2 members of the Rab family of small GTPases, Rab3a and Rab10, are essential for lysosome exocytosis and PMR in cells challenged with a bacterial toxin, streptolysin-O (SLO). Additionally, we showed that Rab3a regulates PMR via the interaction with 2 effectors, synaptotagmin-like protein 4a (Slp4-a) and nonmuscle myosin heavy chain IIA (NMHC IIA), the latter being identified for the first time as a Rab3a effector. This tripartite complex is essential for the positioning of the peripheral lysosomes responsible for PMR. In cells lacking any of the components of this tripartite complex, lysosomes were concentrated in the perinuclear region and absent in the periphery culminating with PMR inhibition.


Rab proteins; lysosome positioning; lysosomes; membrane traffic; plasma membrane repair

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