A recent work showed that downregulation of Rab27a blocked lysosomal exocytosis in Schwann cells and reduced the remyelination of regenerated sciatic nerve, suggesting an important role for Rab27a in remyelination within the peripheral nervous system . In addition, a role for Rab27 isoforms in exosome secretion has also been demonstrated . Rab27a was the first example of a Rab protein implicated in a human genetic disease: Griscelli syndrome type 2 (GS2), a rare autosomal recessive disorder caused by mutations
in the Rab27a gene . Clinical features of this syndrome eFT508 mw include partial albinism and immune disorder. The ashen mouse is the corresponding murine model . In accordance with the location of secretory granules, Rab27a is polarized towards the apical domain of epithelial cells . Rab27a regulates secretion of ATM Kinase Inhibitor clinical trial lysosome-related organelles (LROs), a heterogeneous group of organelles which share features with multivesicular bodies (MVBs)/lysosomes. Nevertheless, although LROs share various features with late endosomes/lysosomes, they
differ in function, morphology, and composition. These organelles include, among others, melanosomes in melanocytes, lytic granules in CTLs, dense granules in platelets, azurophilic granules in neutrophils and eosinophils and Weibel-Palade bodies (WPB) in endothelial cells [27, 28]. Although all these cellular compartments share several characteristics, LROs and classic secretory granules differ in the source of their membrane and lumenal contents: most of LROs content derives from the endosomal system, Capmatinib whereas secretory granules derive directly from the TGN. However, it is now accepted that LROs comprise a very heterogeneous group of organelles that seem to have diverse origins . Several Rab GTPases have been involved in the morphogenesis of herpesviruses. In particular, recent works have revealed the role for Rab1a/b, Rab3a and Rab43 in HSV-1 envelopment [30, 31]. Other Rab proteins, such as Rab6 and Rab27a, have
also been involved in HCMV –a member of the betaherpesvirinae subfamily– assembly [31–33]. Given the similarities in the assembly these processes amongst several members of the Herpesviridae, we investigated the role of Rab27a in HSV-1 morphogenesis. We show that this small GTPase colocalizes in the TGN with the viral glycoproteins gH and gD, together with a pUL46-green fluorescent protein (GFP)-tagged HSV-1 (GHSV-UL46). Moreover, Rab27a depletion decreases the infection rate. Taken together, these data point to a significant role for Rab27a in the infection of oligodendrocytic cells with HSV-1. Results Expression of Rab27a in HOG cells Several reports have previously shown Rab27a expression on many different cell types. However, to date, no study addressed Rab27a expression in oligodendrocytic cultures.