Rab9dependent

Rab9-dependent refers to cellular trafficking pathways that require the small GTPase Rab9 for proper vesicle transport. Rab9 is a member of the Rab family of cytosolic GTPases and is primarily associated with late endosomes and the trans-Golgi network (TGN). In the Rab9-dependent retrograde pathway, cargo is retrieved from late endosomes back to the TGN, enabling recycling of receptors such as the mannose-6-phosphate receptor (MPR) and ensuring efficient delivery of lysosomal hydrolases to lysosomes.

Mechanistically, Rab9 cycles between an active GTP-bound state and an inactive GDP-bound state, a cycle regulated by guanine nucleotide exchange factors and GTPase-activating proteins. In its active form, Rab9 engages effector proteins to promote vesicle formation, cargo selection, and tethering to the TGN membrane. A well-characterized Rab9 effector is TIP47, which binds MPR cargo and supports retrograde trafficking; additional effectors and tethering factors cooperate to facilitate docking and fusion with the TGN.

Significance and regulation of Rab9-dependent transport are tied to lysosome biogenesis and intracellular sorting of lysosomal enzymes. Disruption of Rab9-dependent transport can impair MPR recycling and hydrolase trafficking, with potential impacts on lysosomal function. The Rab9 gene has vertebrate homologs, including Rab9A and Rab9B, reflecting functional conservation and potential tissue-specific roles across species.