EMAIL THIS PAGE TO A FRIEND

Molecular and cellular biology

Leucine-Rich Repeat Kinase 1 Regulates Autophagy through Turning On TBC1D2-Dependent Rab7 Inactivation.


PMID 26100023

Abstract

Autophagy is a conserved process that enables catabolic and degradative pathways. Rab family proteins, which are active in the GTP-bound form, regulate the transport and fusion of autophagosomes. However, it remains unclear how each cycle of Rab activation and inactivation is precisely regulated. Here, we show that leucine-rich repeat kinase 1 (LRRK1) regulates autophagic flux by controlling Rab7 activity in autolysosome formation. Upon induction of autophagy, LRRK1 was recruited via an association with VAMP7 to the autolysosome, where it activated the Rab7 GTPase-activating protein (GAP) TBC1D2, thereby switching off Rab7 signaling. Consistent with this model, LRRK1 deletion caused mice to be vulnerable to starvation and disrupted autolysosome formation, as evidenced by the accumulation of enlarged autolysosomes with undegraded LC3-II and persistently high levels of Rab7-GTP. This defect in autophagic flux was partially rescued by a mutant form of TBC1D2 with elevated Rab7-GAP activity. Thus, the spatiotemporal regulation of Rab7 activity during tunicamycin-induced autophagy is regulated by LRRK1.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1304478
ANTI-ARHGAP22 (C-TERM) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB1407961
Anti-LRRK1 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA010537
Anti-LRRK1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1401828
Anti-LRRK1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB4503168
Anti-LRRK1 antibody produced in rabbit, affinity isolated antibody
R4779
Anti-Rab7 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA006964
Anti-RAB7A antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1411418
Anti-RAB7A antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1400614
Anti-TBC1D2 antibody produced in mouse, IgG fraction of antiserum, buffered aqueous solution
HPA030871
Anti-TBC1D2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA036733
Anti-VAMP7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2106779
Anti-VAMP7 antibody produced in rabbit, affinity isolated antibody
SAB3500844
Anti-VAMP7 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2105695
Anti-VAMP7, (N-terminal) antibody produced in rabbit, affinity isolated antibody
SAB1403894
Monoclonal Anti-GTF2H1, (C-terminal) antibody produced in mouse, clone 4B9, purified immunoglobulin, buffered aqueous solution
SAB1401829 Monoclonal Anti-LRRK1 antibody produced in mouse, clone 3G8, purified immunoglobulin, buffered aqueous solution
R8779
Monoclonal Anti-Rab7 antibody produced in mouse, ~2 mg/mL, clone Rab7-117, purified immunoglobulin, buffered aqueous solution