Kern Andreas, Dikic Ivan, Behl Christian
a Institute for Pathobiochemistry; University Medical Center of the Johannes Gutenberg University ; Mainz , Germany.
b Buchmann Institute for Molecular Life Sciences; Goethe University Frankfurt ; Frankfurt am Main , Germany.
Autophagy. 2015;11(12):2393-7. doi: 10.1080/15548627.2015.1110668.
Macroautophagy is a conserved degradative pathway in which a double-membrane compartment sequesters cytoplasmic cargo and delivers the contents to lysosomes for degradation. Efficient formation and maturation of autophagic vesicles, so-called phagophores that are precursors to autophagosomes, and their subsequent trafficking to lysosomes relies on the activity of small RAB GTPases, which are essential factors of cellular vesicle transport systems. The activity of RAB GTPases is coordinated by upstream factors, which include guanine nucleotide exchange factors (RAB GEFs) and RAB GTPase activating proteins (RAB GAPs). A role in macroautophagy regulation for different TRE2-BUB2-CDC16 (TBC) domain-containing RAB GAPs has been established. Recently, however, a positive modulation of macroautophagy has also been demonstrated for the TBC domain-free RAB3GAP1/2, adding to the family of RAB GAPs that coordinate macroautophagy and additional cellular trafficking pathways.
巨自噬是一种保守的降解途径，其中双膜隔室隔离细胞质货物，并将其内容物输送到溶酶体进行降解。自噬小泡（即自噬体的前体，称为吞噬泡）的有效形成和成熟，以及它们随后向溶酶体的运输依赖于小RAB GTP酶的活性，小RAB GTP酶是细胞囊泡运输系统的关键因素。RAB GTP酶的活性由上游因子协调，上游因子包括鸟嘌呤核苷酸交换因子（RAB GEFs）和RAB GTP酶激活蛋白（RAB GAPs）。已确定不同的含TRE2-BUB2-CDC16（TBC）结构域的RAB GAPs在巨自噬调节中发挥作用。然而，最近还证明了无TBC结构域的RAB3GAP1/2对巨自噬有正向调节作用，这增加了协调巨自噬和其他细胞运输途径的RAB GAPs家族。
