RAB6:GTP and BICD homodimers bind COPI-independent Golgi-to-ER retrograde cargo

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Homo sapiens
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COPI-independent retrograde traffic from the Golgi to the ER depends on RAB6 and involves formation of membrane tubules instead of classical transport vesicles. COPI-dependent and COPI-independent retrograde transport appear to have distinct cargo, as anti-COPI antibodies inhibit the traffic of KDEL-containing receptors, but not that of Shiga or Shiga-like toxins, or of Golgi-resident glycosylation enzymes (White et al, 1999; Girod et al, 1999). It is not yet clear how membrane tubules formation is initiated, however cargo type and concentration, as well as lipid composition may contribute (Martinez et al, 1997; Simpson et al, 2006; de Figueiredo et al, 1998; de Figueiredo et al, 1999; reviewed in Heffernan and Simpson 2014). The presence of sn2-lysophospholipids in the Golgi membrane generates curved membranes that are thought to favour tubule formation. Lysophospholipids are generated by the activity of phopholipase A2 enzymes that hydrolyze the fatty acid at the sn-2 position; this activity is counteracted by the activity of lysophospholipid acyltransferases (LPATs). The balance of these two activities at the Golgi membrane is thought to play a role in determining whether COPI-dependent or -independent transport is favoured (de Figueiredo et al, 1998; de Figueiredo et al, 1999; Schmidt et al, 2009; reviewed in Heffernan and Simpson, 2014). Recent studies have also implicated the coiled coil homodimer Bicaudal-D (BICD) proteins in COPI-independent retrograde traffic. BICD proteins bind RAB6:GTP with their C-terminal ends and the dynein:dynactin motor complex with their N-terminal ends and in this way are thought to facilitate the recruitment of motor proteins to the RAB6 retrograde pathway (Hoogenraad et al, 2001; Matanis et al, 2002; Young et al, 2005; Januschke et al, 2007).

Literature References
PubMed ID Title Journal Year
15483056 Regulation of microtubule-dependent recycling at the trans-Golgi network by Rab6A and Rab6A'

Young, J, Pepperkok, R, Stauber, T, Vernos, I, Nilsson, T, del Nery, E

Mol. Biol. Cell 2005
10562278 Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells

Girod, A, White, J, Grill, S, Reinsch, S, Johannes, L, Stelzer, EH, Keller, P, Tzschaschel, B, Goud, B, Echard, A, Mallard, F

J. Cell Biol. 1999
12447383 Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex

Weide, T, Grosveld, F, Matanis, T, Wulf, P, Barnekow, A, Galjart, N, Akhmanova, A, Stepanova, T, De Zeeuw, CI, Goud, B, Hoogenraad, CC, del Nery, E

Nat. Cell Biol. 2002
11483508 Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes

Grosveld, F, Willemsen, R, Dortland, BR, Visser, P, Howell, SA, Galjart, N, Akhmanova, A, De Zeeuw, CI, Hoogenraad, CC

EMBO J. 2001
9671731 Evidence that phospholipase A2 activity is required for Golgi complex and trans Golgi network membrane tubulation

Drecktrah, D, Katzenellenbogen, JA, Strang, M, Brown, WJ, de Figueiredo, P

Proc. Natl. Acad. Sci. U.S.A. 1998
10359595 Membrane tubule-mediated reassembly and maintenance of the Golgi complex is disrupted by phospholipase A2 antagonists

Drecktrah, D, Polizotto, RS, Brown, WJ, de Figueiredo, P

Mol. Biol. Cell 1999
16314391 Biogenesis of tubular ER-to-Golgi transport intermediates

Simpson, JC, Pepperkok, R, Nilsson, T

Mol. Biol. Cell 2006
9050864 GTP-bound forms of rab6 induce the redistribution of Golgi proteins into the endoplasmic reticulum

Martinez, O, Berger, EG, Pehau-Arnaudet, G, Salamero, J, Goud, B, Antony, C

Proc. Natl. Acad. Sci. U.S.A. 1997
17827179 Rab6 and the secretory pathway affect oocyte polarity in Drosophila

Formstecher, E, Guichet, A, Goud, B, Januschke, J, Compagnon, J, Nicolas, E

Development 2007
25233431 The trials and tubule-ations of Rab6 involvement in Golgi-to-ER retrograde transport

Simpson, JC, Heffernan, LF

Biochem. Soc. Trans. 2014
19635840 Lysophosphatidic acid acyltransferase 3 regulates Golgi complex structure and function

Brown, WJ, Schmidt, JA

J. Cell Biol. 2009
10559986 Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum

Girod, A, Lord, JM, Johannes, L, Simpson, JC, Pepperkok, R, Goud, B, Storrie, B, Nilsson, T, Roberts, LM

Nat. Cell Biol. 1999
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