Prenylation of RabGTPases, Their Delivery to Membranes, and Rab Recycling - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 12

Fig. 1.4 Overview of important factors and principles in Rab targeting. GEF-mediated nucleotide
exchange appears to be the major factor for Initial insertion of Rab proteins into membranes.
Further interactions are probably of importance in determining the steady-state distribution
between membrane and GDI. Note that univalent interaction with an effector will not increase
stability unless there is an additional membrane-anchoring interaction of the effector (direct or
indirect). A bivalent effector interaction of the type depicted could lead to stabilization of the
Rab-membrane interaction, but the targeting step would still be dependent on GEFs.
[Figure modified from Li et al. ( 2014 )]
1.6 Conclusion
The work described briefly here leads to the conclusion that GEFs are major
determinants in Rab targeting, but numerous observations suggest that a model in
which GEFs are the sole determining factor is not correct. In some situations, there
is evidence that effector interactions are important, while other observations
demand another, additional targeting factor or principle. As a working model, we
suggest that GTP/GDP exchange at a specific location plays a crucial role in
targeting, but that additional stabilization of the membrane-bound state occurs in
at least some cases, possibly including formation of a heterotetrameric complex
containing two effector and two Rab molecules. In general, it is appears to be the
interplay of GEFs, GAPs, effectors, and possibly still unrecognized principles that
determines localization in a highly dynamic and complex process.
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