Rif is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rho family of GTPases.[1] It is primarily active in the brain and plays a physiological role in the formation of neuronal dendritic spine. This process is regulated by FARP1, a type of activator for RhoA GTPases.[2] Alternatively, Rif can induce the formation of actin stress fibers in epithelial cells, which is dependent on the activity levels of ROCK proteins since the absence of ROCK activity would mean Rif would be unable to stimulate the growth of stress fibers.[3]

Rif is also seen expressed in diverse amount of human tissues such as in the colon and stomach due to Rho's use of actin dynamics to absorb intestinal epithelial cells.[4] Rif is one way of generating filopodia (Rif-induced filopodia) through its interaction with mDia2. Specifically, the interaction is between the GTP from Rif and the GTPase binding domain (GBD) of mDia2.[3][5] Rif's function in forming filopodia has a relation to the function of platelets. But in mice, Rif is not necessary for platelets to function.[6] The co-expression of Rif with Rac or Cdc42, other GTPases that also participate in regulating cell structure and morphology, can give rise to new filopodial structures that differ from the filopodia arrangements stimulated by each of these GTPases functioning separately.[7]

References

  1. ^ Ridley AJ (October 2006). "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends in Cell Biology. 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. PMID 16949823.
  2. ^ Fan L, Yan H, Pellegrin S, Mellor H (March 2015). "The Rif GTPase regulates cytoskeletal signaling from plexinA4 to promote neurite retraction". Neuroscience Letters. 590: 178–83. doi:10.1016/j.neulet.2015.02.010. PMID 25668492. S2CID 23364498.
  3. ^ a b Fan L, Pellegrin S, Scott A, Mellor H (April 2010). "The small GTPase Rif is an alternative trigger for the formation of actin stress fibers in epithelial cells". Journal of Cell Science. 123 (Pt 8): 1247–52. doi:10.1242/jcs.061754. PMC 2848113. PMID 20233848.
  4. ^ Fan L, Mellor H (February 2012). "The small Rho GTPase Rif and actin cytoskeletal remodelling". Biochemical Society Transactions. 40 (1): 268–72. doi:10.1042/BST20110625. PMID 22260703.
  5. ^ Pellegrin, Stéphanie; Mellor, Harry (2005-01-26). "The Rho Family GTPase Rif Induces Filopodia through mDia2". Current Biology. 15 (2): 129–133. doi:10.1016/j.cub.2005.01.011. ISSN 0960-9822. PMID 15668168. S2CID 16226672.
  6. ^ Goggs R, Savage JS, Mellor H, Poole AW (2013-01-24). "The small GTPase Rif is dispensable for platelet filopodia generation in mice". PLOS ONE. 8 (1): e54663. Bibcode:2013PLoSO...854663G. doi:10.1371/journal.pone.0054663. PMC 3554654. PMID 23359340.
  7. ^ Ellis, Sara; Mellor, Harry (November 2000). "The novel Rho-family GTPase Rif regulates coordinated actin-based membrane rearrangements". Current Biology. 10 (21): 1387–1390. doi:10.1016/s0960-9822(00)00777-6. ISSN 0960-9822. PMID 11084341. S2CID 18415070.



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