Rab Proteins and the Organization of Organelle Membrane Domains - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 31

Whereas most membrane domain models are derived from the study of individ-
ual protein-protein interactions and crude biochemical approaches, little is known
how Rab GTPases and Rab effectors are organized spatially. Research in this
direction is hampered by the technical limitation of standard light microscopes.
Both the size of membrane domains and the distance between two distinct mem-
brane domains are below the 200 nm diffraction limit of fluorescent microscopes
and can therefore not be resolved. Fortunately, the recent advances in super-
resolution microscopy and correlative light-electron microscopy (CLEM) (Hensel
et al. 2013 ) provide a means to study this problem.
Most cell biological research on Rab domain localization and dynamics is
performed in mammalian dedifferentiated tissue culture cells. Combined with the
biochemical approaches discussed above, tissue culture cells have been extremely
useful for the identification of basic aspects of domain formation; however, they
poorly represent the complex nature of physiological cells in three-dimensional
tissue. Therefore, future research on Rab GTPases and their membrane domains
should increasingly focus on cells in a three-dimensional tissue context and living
vertebrate model system (Weigert et al. 2013 ).
References
Abankwa D, Gorfe A, Hancock J (2008) Mechanisms of Ras membrane organization and
signaling: Ras on a rocker. Cell Cycle 7(17):2667-2673
Bache KG, Raiborg C, Mehlum A, Madshus IH, Stenmark H (2002) Phosphorylation of Hrs
downstream of the epidermal growth factor receptor. Eur J Biochem 269(16):3881-3887
Backer JM (2008) The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem
J 410(1):1-17
Barbero P, Bittova L, Pfeffer SR (2002) Visualization of Rab9-mediated vesicle transport from
endosomes to the trans-Golgi in living cells. J Cell Biol 156(3):511-518
Barr FA (2013) Rab GTPases and membrane identity: causal or inconsequential? J Cell Biol 202
(2):191-199
Barr F, Lambright DG (2010) Rab GEFs and GAPs. Curr Opin Cell Biol 22(4):461-470
Bl¨mer J, Rey J, Dehmelt L, Mazel T, Wu Y-W, Bastiaens P, Goody RS, Itzen A (2013) RabGEFs
are a major determinant for specific Rab membrane targeting. J Cell Biol 200(3):287-300
Bonifacino JS, Glick BS (2004) The mechanisms of vesicle budding and fusion. Cell 116
(2):153-166
Bonifacino JS, Hierro A (2011) Transport according to GARP: receiving retrograde cargo at the
trans-Golgi network. Trends Cell Biol 21(3):159-167
Brandhorst D, Zwilling D, Rizzoli SO, Lippert U, Lang T, Jahn R (2006) Homotypic fusion of
early endosomes: SNAREs do not determine fusion specificity. Proc Natl Acad Sci USA 103
(8):2701-2706
Brandman O, Meyer T (2008) Feedback loops shape cellular signals in space and time. Science
322(5900):390-395
Br¨cker C, Engelbrecht-Vandr´ S, Ungermann C (2010) Multisubunit tethering complexes and
their role in membrane fusion. Curr Biol 20(21):R943-R952
Br¨cker C, Kuhlee A, Gatsogiannis C, Kleine Balderhaar HJ, H¨nscher C, Engelbrecht-Vandr´ S,
Ungermann C, Raunser S (2012) Molecular architecture of the multisubunit homotypic fusion