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Cargo trafficking to the periciliary membrane

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-5620920

PubChem

R-HSA-5620920

Description

Proteomic studies suggest that the cilium is home to approximately a thousand proteins, and has a unique protein and lipid make up relative to the bulk cytoplasm and plasma membrane (Pazour et al, 2005; Ishikawa et al, 2012; Ostrowoski et al, 2002; reviewed in Emmer et al, 2010; Rohatgi and Snell, 2010). In addition, the cilium is a dynamic structure, and the axoneme is continually being remodeled by addition and removal of tubulin at the distal tip (Marshall and Rosenbaum, 2001; Stephens, 1997; Song et al, 2001). As a result, the function and structure of this organelle relies on the directed trafficking of protein and vesicles to the cilium. Small GTPases of the RAS, RAB, ARF and ARL families are involved in cytoskeletal organization and membrane traffic and are required to regulate the traffic from the Golgi and the trans-Golgi network to the cilium (reviewed in Deretic, 2013; Li et al, 2012). ARF4 is a Golgi-resident GTPase that acts in conjunction with a ciliary-targeting complex consisting of the ARF-GAP ASAP1, RAB11A, the RAB11 effector FIP3 and the RAB8A guanine nucleotide exchange factor RAB3IP/RABIN8 to target cargo bearing a putative C-terminal VxPx targeting motif to the cilium. A well-studied example of this system involves the trafficking of rhodopsin to the retinal rod photoreceptors, a specialized form of the cilium (reviewed in Deretic, 2013). ARL3, ARL13B and ARL6 are all small ARF-like GTPases with assorted roles in ciliary trafficking and maintenance. Studies in C. elegans suggest that ARL3 and ARL13B have opposing roles in maintaining the stability of the anterograde IFT trains in the cilium (Li et al, 2010). In addition, both ARL3 and ARL13B have roles in facilitating the traffic of subsets of ciliary cargo to the cilium. Myristoylated cargo such as peripheral membrane protein Nephrocystin-3 (NPHP3) is targeted to the cilium in a UNC119- and ARL3-dependent manner, while ARL13B is required for the PDE6-dependent ciliary localization of INPP5E (Wright et al, 2011; Humbert et al, 2012; reviewed in Li et al, 2012). ARL6 was also identified as BBS3, a gene that when mutated gives rise to the ciliopathy Bardet-Biedl syndrome (BBS). ARL6 acts upstream of a complex of 8 other BBS-associated proteins known as the BBSome. ARL6 and the BBSome are required for the ciliary targeting of proteins including the melanin concentrating hormone receptor (MCHR) and the somatostatin receptor (SSTR3), among others (Nachury et al, 2007; Loktev et al, 2008; Jin et al, 2010; Zhang et al, 2011). Both the BBSome and ARL6 may continue to be associated with cargo inside the cilium, as they are observed to undergo typical IFT movements along the axoneme (Fan et al, 2004; Lechtreck et al, 2009; reviewed in Li et al, 2012).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
A6NNZ2	Tubulin beta 8B	TUBB8B	view
P04350	Tubulin beta-4A chain	TUBB4 TUBB4A TUBB5	view
P68363	Tubulin alpha-1B chain	TUBA1B	view
P68366	Tubulin alpha-4A chain	TUBA1 TUBA4A	view
P68371	Tubulin beta-4B chain	TUBB2C TUBB4B	view
Q13509	Tubulin beta-3 chain	TUBB3 TUBB4	view
Q13885	Tubulin beta-2A chain	TUBB2 TUBB2A	view
Q71U36	Tubulin alpha-1A chain	TUBA1A TUBA3	view
Q9BQE3	Tubulin alpha-1C chain	TUBA1C TUBA6	view
Q9BUF5	Tubulin beta-6 chain	TUBB6	view

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