Modulation of small GTPases by Legionella

TY - JOUR

T1 - Modulation of small GTPases by Legionella

AU - Goody, Roger S

AU - Itzen, Aymelt

PY - 2013

Y1 - 2013

N2 - The pathogenic bacterium Legionella pneumophila interacts intimately with signaling molecules during the infection of eukaryotic host cells. Among a diverse set of regulatory molecules, host small GTPases appear to be prominent and significant targets. Small GTPases are molecular switches that regulate cellular signaling via their respective nucleotide-bound states: When bound to GDP, they are inactive, but become activated upon binding to GTP. Legionella secretes specific bacterial proteins into the cytosol of the host cell that most prominently modulate the activities of small GTPases involved in vesicular trafficking, but probably also other G-proteins. The master regulators of vesicular trafficking, i.e., Rab and Arf proteins, are majorly targeted G-proteins of Legionella proteins, and among these, Rab1 experiences the most diverse modifications. Generally, the activities of small GTPases are modulated by GDP/GTP exchange (activation), GTP hydrolysis (deactivation), membrane recruitment, post-translational modifications (phosphocholination, adenylylation), and tight and competitive binding. Here, we discuss the consequences and molecular details of the modulation of small GTPases for the infection by Legionella, with a special but not exclusive focus on Rab and Arf proteins.

AB - The pathogenic bacterium Legionella pneumophila interacts intimately with signaling molecules during the infection of eukaryotic host cells. Among a diverse set of regulatory molecules, host small GTPases appear to be prominent and significant targets. Small GTPases are molecular switches that regulate cellular signaling via their respective nucleotide-bound states: When bound to GDP, they are inactive, but become activated upon binding to GTP. Legionella secretes specific bacterial proteins into the cytosol of the host cell that most prominently modulate the activities of small GTPases involved in vesicular trafficking, but probably also other G-proteins. The master regulators of vesicular trafficking, i.e., Rab and Arf proteins, are majorly targeted G-proteins of Legionella proteins, and among these, Rab1 experiences the most diverse modifications. Generally, the activities of small GTPases are modulated by GDP/GTP exchange (activation), GTP hydrolysis (deactivation), membrane recruitment, post-translational modifications (phosphocholination, adenylylation), and tight and competitive binding. Here, we discuss the consequences and molecular details of the modulation of small GTPases for the infection by Legionella, with a special but not exclusive focus on Rab and Arf proteins.

KW - ADP-Ribosylation Factor 1

KW - Humans

KW - Legionella

KW - Monomeric GTP-Binding Proteins

KW - rab1 GTP-Binding Proteins

KW - Journal Article

KW - Review

U2 - 10.1007/82_2013_340

DO - 10.1007/82_2013_340

M3 - SCORING: Review article

C2 - 23918171

VL - 376

SP - 117

EP - 133

JO - CURR TOP MICROBIOL

JF - CURR TOP MICROBIOL

SN - 0070-217X

ER -