ARF-Like (ARL) Proteins - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 215

localization of ARFs to the Golgi was also observed in cells expressing ARL1
[Q71L]. This effect appeared to be specific to the Golgi as localization of COPII at
the endoplasmic reticulum and -adaptin at the plasma membrane was unaltered by

ARL1[Q71L] expression. Brefeldin A treatment typically results in the loss of
Golgi-associated AP-1, COPI, and ARFs; however, these proteins were retained
at the Golgi in ARL1[Q71L]-expressing cells treated with brefeldin A
(Lu et al. 2001 ). These data suggest a role for ARL1 in the recruitment of AP-1,
COPI, and ARFs to the Golgi, though this recruitment appears to be indirect as the
brefeldin A-induced cytosolic redistribution of these proteins does not coincide
with ARL1 (Lowe et al. 1996 ).
The list of ARL1 effectors continues to increase and includes the GRIP domain
containing Golgins, the ARF GEFs BIG1/2, and interesting but confusing links to
the yeast phospholipid flippase DRS2. It is quite possible that the brefeldin A
sensitivities of ARL1, which again are quite similar but temporally distinct from
those of ARFs, result from the binding and role of ARL1 in recruiting BIGs to
membranes. ARL1 recruits the ARF GEFs, BIG1 and BIG2, to the trans -Golgi
(Christis and Munro 2012 ), thereby acting upstream of ARF activation at the Golgi.
This direct binding of ARL1 to an ARF GEF is conserved in yeast as it also was
found to bind the ortholog of the BIGs, GEA2 (Tsai et al. 2013 ). ARL1 also
interacts with and recruits several other proteins to the Golgi apparatus. Yeast
two-hybrid screens using the GTPase-defective mutant of ARL1 identified multiple
ARL1 binding partners, including PDE

α

, SCOCO, Arfaptin 2/POR1, pericentrin,
and MLKP1, a subset of which are shared effectors for ARF1 (Lu et al. 2001 ; Van
Valkenburgh et al. 2001 ). ARL1 directly interacts with a glutamate receptor-
interacting protein (GRIP) domain to facilitate the recruitment of Golgi-associated
proteins, namely, members of the Golgin family (Munro and Nichols 1999 b; Van
Valkenburgh et al. 2001 ; Lu and Hong 2003 ; Lu et al. 2005 ). Structural studies
revealed that the C-terminal GRIP domain of Golgin-245 forms a homodimer that
interacts with two molecules of ARL1-GTP (Panic et al. 2003 ; Wu et al. 2004 ),
leaving the N-terminal coiled-coil region to project into the cytosol and function in
effector recruitment. And analogous in a very general way to the important role that
phospholipids play in ARF activities, Lu et al. ( 2006 ) found that lipids are also an
essential component in the ARL1-dependent recruitment of Golgins. Knockdown
of ARL1 or Golgin-97 in HeLa cells inhibited retrograde transport from the
endosome to the Golgi, suggesting that ARL1 and Golgin-97 act as a tethering
complex in endosome-to-Golgi trafficking (Lu et al. 2004 ). Importantly, members
of two laboratories discovered that ARL1 acts in close conjunction with another
family member, ARFRP1, in what may ultimately prove to be a hallmark of the
family: GTPase cascades or pathways involving two or more ARF family members.

ʴ