The dynamic Rab11-FIPs.

Molecular Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
Biochemical Society Transactions (Impact Factor: 2.59). 10/2009; 37(Pt 5):1032-6. DOI: 10.1042/BST0371032
Source: PubMed

ABSTRACT The Rab11-FIPs (Rab11-family interacting proteins; also known as FIPs) constitute an evolutionarily conserved protein family that act as effector molecules for multiple Rab and Arf (ADP-ribosylation factor) GTPases. They were initially characterized by their ability to bind Rab11 subfamily members via a highly-conserved C-terminal RBD (Rab11-binding domain). Resolution of the crystal structure of Rab11 in complex with FIPs revealed that the RBD mediates homodimerization of the FIP molecules, creating two symmetrical interfaces for Rab11 binding and leading to the formation of a heterotetrameric complex between two FIP and two Rab11 molecules. The FIP proteins are encoded by five genes and alternative splicing has been reported. Based on primary structure, the FIPs were subcategorized into two classes: class I [Rip11, FIP2 and RCP (Rab-coupling protein)] and class II (FIP3 and FIP4). Recent studies have identified the FIPs as key players in the regulation of multiple distinct membrane trafficking events. In this mini-review, we summarize the Rab11-FIP field and discuss, at molecular and cellular levels, the recent findings on FIP function.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: cGMP-dependent protein kinase (PKG) interacting proteins (GKIPs) mediate cellular targeting of PKG isoforms by interacting with their leucine zipper (LZ) domains. These interactions prevent aberrant signaling cross talk between different PKG isotypes. To gain detailed insight into isotype-specific GKIP recognition by PKG, we analyzed the type II PKG LZ domain and found that residues 40 to 83 dimerized and specifically interacted with Rab11b. Next, we determined a crystal structure of the PKG II LZ-Rab11b complex. The PKG II LZ domain presents a mostly nonpolar surface onto which Rab11b docks, through Van der Waals interactions. Contact surfaces in Rab11b are found in the switch I, II, interswitch, and the β1/N-terminal regions. This binding surface dramatically differs from that seen in Rab11-FIP complex structures. Structural comparison with PKG Iα and Iβ LZs combined with mutagenic analysis reveals that GKIP recognition is mediated through surface charge interactions.
    Journal of Biological Chemistry 07/2014; · 4.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rab11a is a key modulator of vesicular trafficking processes, but there is limited information about the guanine nucleotide-exchange factors and GTPase-activating proteins (GAPs) that regulate its GTP-GDP cycle. We observed that in the presence of Mg(2+) (2.5 mM) TBC1D9B interacted via its TBC (Tre2-Bub2-Cdc16) domain with Rab11a, Rab11b, and Rab4a in a nucleotide-dependent manner. However, only Rab11a was a substrate for TBC1D9B-stimulated GTP hydrolysis. At limiting Mg(2+) concentrations (< 0.5 mM), Rab8a was an additional substrate for this GAP. In polarized Madin-Darby canine kidney cells, endogenous TBC1D9B colocalized with Rab11a-positive recycling endosomes, but less so with EEA1-positive early endosomes, transferrin-positive recycling endosomes, or late endosomes. Overexpression of TBC1D9B, but not an inactive mutant, decreased the rate of basolateral-to-apical IgA transcytosis, a Rab11a-dependent pathway, and shRNA-mediated depletion of TBC1D9B increased the rate of this process. In contrast, TBC1D9B had no effect on two Rab11a-independent pathways, basolateral recycling of the transferrin receptor or degradation of the epidermal growth factor receptor. Finally, expression of TBC1D9B decreased the amount of active Rab11a in the cell, and concomitantly disrupted the interaction between Rab11a and its effector Sec15A. We conclude that TBC1D9B is a Rab11a GAP that regulates basolateral-to-apical transcytosis in polarized MDCK cells.
    Molecular Biology of the Cell 09/2014; 25(23). · 4.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the Drosophila photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of Crag or Rab11 leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of Crag can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport. Copyright: ß 2012 Xiong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding:. H.J.B. is an investigator of the HHMI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
    PLoS Biology 12/2012; 2(6). · 11.77 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014