Biology Reference
In-Depth Information
1992
). In addition, knock-out mice for cytoplasmic dynein 1 (CD1), a TGN-
associated dynein (Fath et al.
1994
), developed into the blastocyst stage before
embryonic death and reabsorption. Cells recovered from this CD1 knockout
blastocyst had fragmented Golgi membranes in the form of peripheral mini-stacks
(Harada et al.
1998
). Another dynein family member, cytoplasmic dynein 2 (CD2),
also localized to the Golgi apparatus, although its distribution was more ubiquitous
than that of CD1 (Vaisberg et al.
1996
). Blocking CD2 function by microinjection
of a specific monoclonal antibody resulted in the conversion of the Golgi ribbon
into peripheral mini-stacks. Similarly, interfering with the function of the minus-
end directed kinesin family member KIFC3 caused Golgi fragmentation (Xu et al.
2002
). These experiments provide strong support for a role of minus-end directed
microtubule motors in Golgi organization and position.
The motor protein kinesin, which, in general, moves toward microtubule plus-
ends, are also important for the maintenance of Golgi organization. Indeed, ki-
nesins have been proposed to provide an opposing force to dyneins. Similar to
what has been observed for dyneins, various kinesin family members localize to
the Golgi (Allan et al.
2002
; Gyoeva et al.
2000
; Lippincott-Schwartz et al.
1995
;
Thyberg and Moskalewski
1999
). Their RNAi-mediated knockdown resulted in
the collapse of the Golgi into a circular body in the cell center, with reduction in
the overall size, number, and spreading of Golgi cisternae (Feiguin et al.
1994
).
Thus, a balance between dynein and kinesin activity may be the critical deter-
minant for the pericentrosomal organization of the Golgi ribbon.
In addition, there are reports implicating the actin cytoskeleton in the mainte-
nance of a pericentrosomal Golgi apparatus. Disruption of actin filaments, spe-
cifically of branched actin structures, resulted in a collapse of Golgi morphology
(di Campli et al.
1999
). Under these conditions, Golgi cisternae remained in a
stacked conformation, but they were swollen and condensed around the nucleus
(Valderrama et al.
1998
). This phenotype was reminiscent of Golgi morphology in
cells with disrupted kinesin activity, suggesting that actin filaments, just like ki-
nesins, may be antagonistic to dynein activity. It is possible that actin filaments
oppose dynein activity by attaching to the plasma membrane, generating tension
and encouraging lateral spreading of Golgi membranes.
Actin can also control Golgi organization through its interacting proteins
spectrin and ankyrin, which have both been detected on the Golgi (Beck
2005
;
Beck et al.
1994
,
1997
; Devarajan et al.
1996
; Fath et al.
1994
; Stankewich et al.
1998
). Spectrin is a cytoskeletal protein that is known to control membrane
organization, stability, and shape by linking membranes to motor proteins or other
cytoskeletal elements. Spectrin binds to membranes via the adaptor protein
ankyrin, which itself associates with integral membrane proteins or membrane
phospholipids. Membrane-bound spectrin-ankyrin complexes are cross-linked by
short actin filaments, creating a flexible meshwork across the surface of a mem-
brane (De Matteis and Morrow
2000
; Godi et al.
1998
). At the plasma membrane,
the spectrin network has been found to promote the formation of specialized
membrane domains by preventing the free diffusion of integral membrane proteins
(Holleran and Holzbaur
1998
). Spectrin and ankyrin may have an analogous role
