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The Exocytosis Regulator Synaptotagmin V Controls Phagocytosis in Macrophages¹

Adrien F. Vinet^*, Mitsunori Fukuda and Albert Descoteaux^2,*

^* Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, Laval, Quebec, Canada; and Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan

Synaptotagmins (Syts) play a key role in the regulation of Ca²⁺-triggered exocytosis and membrane fusion events, two crucial events associated to the phagocytic process. In the present study, we investigated the role of Syt V, a regulator of focal exocytosis, in phagocytosis. In macrophages, Syt V is localized on recycling endosomes and on filopodia-like structures and is recruited to the nascent phagosomes independently of the phagocytic receptor engaged. Silencing of Syt V by RNA interference revealed a role for this protein for phagocytosis, particularly under conditions of high membrane demand. In contrast, silencing of Syt V had no effect on the recruitment of the lysosomal marker LAMP1 to phagosomes, indicating that phagosome maturation is not regulated by Syt V. Collectively, these results illustrate the importance of Syt V in the regulation of an important innate function of macrophages. Furthermore, our results are consistent with the concept that focal exocytosis of endocytic organelles is a key event in phagocytosis and suggest that Syt V regulates this process.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Canadian Institutes of Health Research Grant MT-29033. A.D. is a chercheur-boursier of the Fonds de la recherche en santé du Québec and the holder of a Canada Research Chair. A.F.V. was partly supported by a doctoral fellowship from the Fondation Armand-Frappier.

² Address correspondence and reprint requests to Dr. Albert Descoteaux, Institut National de la Recherche Scientifique-Institut Armand-Frappier, 531 boul des Prairies, Laval, Quebec, Canada H7V 1B7. E-mail address: albert.descoteaux{at}iaf.inrs.ca

³ Abbreviations used in this paper: SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor; IgG-SRBC, IgG-opsonized SRBC; PEM, peritoneal exudate macrophage; PKC, protein kinase C; siRNA, small interfering RNA; RNAi, RNA interference; Syt, synaptotagmin.