Rab coupling protein is associated to phagosomes and regulates phagocytosis

PAVAROTTI M; LEIVA N; COLOMBO MI; DAMIANI MT

Bariloche. Río Negro. Argentina.

Congreso; XXXIX Reunión Científica Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular. SAIB; 2003

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular. SAIB

Rab coupling protein (RCP) is a novel identified protein, that belongs to the Rab11-FIP family. RCP interacts specifically with Rab4 and Rab11, small GTPases that function as regulators along the endosomal recycling pathway. We used fluorescence confocal microscopy and biochemical approaches to evaluate the participation of RCP during particle uptake and phagosome maturation. In macrophages, RCP is predominantly membrane-bound and displays a punctate vesicular pattern throughout the cytoplasm. RCP colocalizes with the transferring receptor and does not colocalize with lysotracker, a marker of lysosomes. Overexpression of H13, the carboxyl-terminal region of RCP which contains the rab binding domain, results in an abnormal endosomal compartment. We found that RCP is associated as discrete patches to early phagosomal membranes and to recycling vesicles departing from phagosomes. In macrophages, overexpression of full-length RCP stimulates the recycling pathway, while overexpression of H13 diminishes this vesicular transport step. This truncated form of RCP is probably acting in a dominant-negative manner by sequestering Rab4/Rab11 in a nonfunctional complex, thus preventing their interaction with endogenous RCP. RCP is an example of a putative effector protein that interacts with more than one RabGTPase and it is likely that RCP acting as an intermediate between Rab4 and Rab11, regulates the vesicular transport along the recycling pathway.