Rab proteins as major determinants of the Golgi complex structure

Figures & data

Figure 1. Illustrative shared and distinguishing traits of Golgi important Rab proteins. Rab proteins share a GTPase cycle between nucleotide-bound, membreane associated and –free states and functional amino acid motifs colored as indicated in (A). However, activated Rab proteins recruit distinct effectors to regulate their respective pathways (B). As indicated in (C). Rab proteins have distinct locations with respect to the Golgi complex and vary in abundance as quantified for purified cell fractions.^{8,10,13,15,17,19,21,22,28,30,39,40,41,54,56,57,58,68,76,79,86,90,93,94}

Table 1. Effect of altered rab expression on golgi ribbon organization.

	Golgi organization
	Overexpresssion			KD/KO/Natural Mutation(s)
Rab Localization	Wild Type Rab	GTP-bound Rab	GDP-bound Rab	KD	KO	Mutation
Pre-Golgi and cis-Golgi
Rab1	Golgi stable	Golgi unstable Golgi ribbon frag-mentation	Golgi unstable, Golgi ribbon frag-mentation	KD similar to overexpression results		NR
Rab2	Overexpression of the Rab2 GAP results in the accumu-lation of Golgi proteins in the ER.			Golgi ribbon fragments in response to Rab2a and Rab2b knockdown.
Rab18	Golgi protein accumulation near ER exit sites with WT or GTP-bound Rab18		Golgi stable
Rab41/Rab6dGolgi	Golgi stable	Golgi stable	Golgi ribbon fragmentation	KD, one report of Golgi fragmentation and another of no effect
Rab43	Golgi frag-nentation		Golgi proteins redistribute to ER exit site adjacent
Late Golgi/TGN and post Golgi	In most cases, depletion or alteration in function of these Rabs has little to no effect on Golgi organization. Summary outcomes are given for only those Rabs having a distinct effect.
Rab3				KD of any of the 4 family members produces Golgi fragmentation
Rab7b
Rab8				Rab8a KD, one report Golgi fragmentation
Rab9a/b
Rab10
Rab11a
Rab13
Rab14
Rab21
Rab22b/Rab31	Golgi stable	Golgi stable	TGN46 distribu-tion disrupted	KD similar to overexpression results
Rab29			Golgi unstable, TGN fragmentation	KD similar to overexpression results
Rab39a
“Bona fide” Golgi cisternal association
	For most of these Rab proteins, there has been little to no investigation of their role in Golgi organization and the reader is referred to high content screen data studies such as that by Galea and Simpson (2015). We summarize here the results of multiple studies for Rab6 and Rab33b.
Rab6	Golgi unstable Proteins relo-cate to ER	Golgi unstable Proteins relo- cate to ER	Golgi stable, if anything, more compact	Golgi stable, by EM longer stacks	KO embry-onically lethal in mice, longer Golgi stacks in MEFs	NR
Rab19
Rab30
Rab33b	Golgi stable	Golgi unstable Golgi frag- mentation and Golgi proteins relo-cate to ER	Golgi stable	Golgi stable	NR	Rab protein mutations destabilizing mutations fragment Golgi and cause skeletal deformations in humans
Rab34
Rab36
Rab39b

Abbreviations

KD, knockdown; KO, knockout; MEF, mouse embryonic fibroblasts; NR, no report

References

Pre-Golgi and cis Golgi Rabs

Rab1;^{1,5,25,61,66,88,96} Rab2;^32,25,1 Rab18;¹⁴ Rab41/Rab6d;⁴² Rab43.^14,23,12

Late Golgi/TGN and post Golgi Rabs

Rab3;²⁵ Rab8b;¹ Rab21;²⁵ Rab22b/Rab31;⁵⁹ Rab29.⁹¹

“Bona fide” Golgi cisternal associated Rabs

Rab6:^6,49,84; Rab33b.^{91,36,81,3,18,70}

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