Rab coupling protein associates with phagosomes and regulates recycling from the phagosomal compartment.
The Rab coupling protein (RCP) is a recently identified novel protein that belongs to the Rab11-FIP family. RCP interacts specifically with Rab4 and Rab11, small guanosine-5'-triphosphatases 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 punctuate vesicular pattern throughout the cytoplasm. RCP is mainly associated with transferrin-containing structures and Rab11-labeled endosomes. Overexpression of H13, the carboxyl-terminal region of RCP that contains the Rab binding domain, results in an abnormal endosomal compartment. Interestingly, we found that RCP is associated as discrete patches or protein domains to early phagosomal membranes. In macrophages, overexpression of full-length RCP stimulates recycling from the phagosomal compartment, whereas overexpression of H13 diminishes this vesicular transport step. It is likely that acting as an intermediate between Rab4 and Rab11, RCP regulates membrane flux along the phagocytic pathway via recycling events.
Damiani
María T
MT
Laboratorio de Biología Celular, Instituto de Histología y Embriología, Facultad de Ciencias Mèdicas, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina. tdamiani@fcm.uncu.edu.ar
Pavarotti
Martín
M
Leiva
Natalia
N
Lindsay
Andrew J
AJ
McCaffrey
Mary W
MW
Colombo
Maria I
MI
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003001:Cloning, Molecular; D011992:Endosomes / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008565:Membrane Proteins; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C488966:RAB11FIP1 protein, human