title: Mycobacterium tuberculosis and Legionella pneumophila phagosomes exhibit arrested maturation despite acquisition of Rab7.
abstract: Rab7 is a small GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. Phagosomes containing inert particles have also been shown to transiently acquire Rab7 as they mature. Disruption in the pathway prior to the acquisition of Rab7 has been suggested as playing a role in the altered maturation of Mycobacterium bovis BCG phagosomes. As a first step to determine whether disruption in the delivery or function of Rab7 could play a role in the altered maturation of Legionella pneumophila and M. tuberculosis phagosomes, we have examined the distribution of wild-type Rab7 and the GTPase-deficient, constitutively active mutant form of Rab7 in HeLa cells infected with L. pneumophila or M. tuberculosis. We have found that the majority of L. pneumophila and M. tuberculosis phagosomes acquire relatively abundant staining for Rab7 and for the constitutively active mutant Rab7 in HeLa cells that overexpress these proteins. Nevertheless, despite acquisition of wild-type or constitutively active Rab7, both the L. pneumophila and the M. tuberculosis phagosomes continue to exhibit altered maturation as manifested by a failure to acquire lysosome-associated membrane glycoprotein 1. These results demonstrate that L. pneumophila and M. tuberculosis phagosomes have receptors for Rab7 and that the altered maturation of these phagosomes is not due to a failure to acquire Rab7.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UCLA School of Medicine, Center for Health Sciences, Los Angeles, California 90095, USA. dclemens@mednet.ucla.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Clemens
authors.forename: B Y
authors.initials: BY
authors.lastname: Lee
authors.forename: M A
authors.initials: MA
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010588:Phagosomes / Q000502:physiology*; D017527:Receptor, IGF Type 2 / Q000032:analysis; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D017527:Receptor, IGF Type 2; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; D020691:rab GTP-Binding Proteins