Reactome | DENND3 exchanges GTP for GDP on RAB12

DENND3 exchanges GTP for GDP on RAB12

Stable Identifier

R-HSA-8876454

Type

Reaction [transition]

Species

Homo sapiens

Compartment

recycling endosome membrane, cytosol

ReviewStatus

5/5

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DENND3 is a RAB12-specific GEF with roles in macroautophagy and the trafficking of proteins from the recycling endosome to the lysosome (Yoshimura et al, 2010; Matsui et al, 2014; Xu et al, 2015; reviewed in Xu and McPherson, 2015). DENND3 activity promotes the formation of active RAB12:GTP, required for the constitutive degradation of plasma membrane proteins such as the transferrin receptor and the amino acid transporter SLC36A4, also known as PAT4 (Matsui et al, 2011; Matsui and Fukuda, 2013; Matsui et al, 2014; Sirohi et al, 2013). Under starvation conditions, DENND3 is phosphorylated by the macroautophagy-promoting kinase ULK1. DENND3- and RAB12-dependent degradation of SLC36A4 contributes to the activation of the macroautophagy pathway by decreasing intracellular amino-acid levels and inhibiting mTORC1 (Matsui and Fukuda, 2013; Matsui et al, 2014; Xu et al, 2015; Fan et al, 2016; reviewed in Xu and McPherson, 2015).

Literature References

PubMed ID	Title	Journal	Year
26177209	DENND3: a signaling/trafficking interface in autophagy McPherson, PS, Xu, J	Cell Cycle	2015
25925668	Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy Fotouhi, M, McPherson, PS, Xu, J	EMBO Rep.	2015
23478338	Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4 Fukuda, M, Matsui, T	EMBO Rep.	2013
21718402	Small GTPase Rab12 regulates constitutive degradation of transferrin receptor Fukuda, M, Itoh, T, Matsui, T	Traffic	2011
20937701	Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors Linford, A, Rigden, DJ, Barr, FA, Gerondopoulos, A, Yoshimura, S	J. Cell Biol.	2010
25341920	Rab proteins and the compartmentalization of the endosomal system Wandinger-Ness, A, Zerial, M	Cold Spring Harb Perspect Biol	2014
26434594	PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer Snell, C, Perera, SM, Azad, A, Goberdhan, DC, Harris, AL, Li, JL, Turley, H, Fan, SJ, McCormick, R, Kazi, S, Wilson, C, Heublein, S	Oncogene	2016
24719330	Dennd3 functions as a guanine nucleotide exchange factor for small GTPase Rab12 in mouse embryonic fibroblasts Fukuda, M, Noguchi, K, Matsui, T	J. Biol. Chem.	2014
27246931	Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases Oguchi, ME, Fukuda, M, Ishida, M	Cell Struct. Funct.	2016
23357852	M98K-OPTN induces transferrin receptor degradation and RAB12-mediated autophagic death in retinal ganglion cells Chalasani, ML, Radha, V, Kumari, A, Swarup, G, Sudhakar, C, Sirohi, K	Autophagy	2013