Increased expression of Rab5a correlates directly with accelerated maturation of Listeria monocytogenes phagosomes.
Previous studies have shown that Listeria monocytogenes (LM) modulates phagocytic membrane traffic. Here we explore whether Rab5a, a GTPase associated with phagosome-endosome fusion, is related to phagosome maturation and to the intracellular survival of LM. Stable transfection of Rab5a cDNA into macrophages accelerates intracellular degradation of LM. Morphological studies confirmed that phagosome maturation and phagosome-lysosome fusion is enhanced by overexpression of Rab5a. Down-regulation experiments using antisense oligonucleotides targeted to the Rab5a mRNA efficiently reduced Rab5a synthesis, reduced phagosome-endosome traffic, blocked phagosome-lysosome fusion, and extended intraphagosomal survival of LM. Down-regulation of Rab5a had no effect on LM internalization. Down-regulation of Rab5c had no effect on phagosome maturation and phagosome-lysosome fusion. The results indicate that Rab5a controls early phagosome-endosome interactions and governs the maturation of the early phagosome leading to phagosome-lysosome fusion.
Alvarez-Dominguez
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Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Stahl
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D000595:Amino Acid Sequence; D001483:Base Sequence; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000378:metabolism* / Q000382:microbiology; D020696:rab5 GTP-Binding Proteins
D019204:GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins