Article

Crag regulates epithelial architecture and polarized deposition of basement membrane proteins in Drosophila.

Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Developmental Cell (Impact Factor: 10.37). 04/2008; 14(3):354-64. DOI: 10.1016/j.devcel.2007.12.012
Source: PubMed

ABSTRACT The polarized architecture of epithelia relies on an interplay between the cytoskeleton, the trafficking machinery, and cell-cell and cell-matrix adhesion. Specifically, contact with the basement membrane (BM), an extracellular matrix underlying the basal side of epithelia, is important for cell polarity. However, little is known about how BM proteins themselves achieve a polarized distribution. In a genetic screen in the Drosophila follicular epithelium, we identified mutations in Crag, which encodes a conserved protein with domains implicated in membrane trafficking. Follicle cells mutant for Crag lose epithelial integrity and frequently become invasive. The loss of Crag leads to the anomalous accumulation of BM components on both sides of epithelial cells without directly affecting the distribution of apical or basolateral membrane proteins. This defect is not generally observed in mutants affecting epithelial integrity. We propose that Crag plays a unique role in organizing epithelial architecture by regulating the polarized secretion of BM proteins.

0 Bookmarks
 · 
101 Views
  • 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
  • [Show abstract] [Hide abstract]
    ABSTRACT: The basement membrane (BM), a specialized sheet of the extracellular matrix contacting the basal side of epithelial tissues, plays an important role in the control of the polarized structure of epithelial cells. However, little is known about how BM proteins themselves achieve a polarized distribution. Here, we identify phosphatidylinositol 4,5-bisphosphate (PIP2) as a critical regulator of the polarized secretion of BM proteins. A decrease of PIP2 levels, in particular through mutations in Phosphatidylinositol synthase (Pis) and other members of the phosphoinositide pathway, leads to the aberrant accumulation of BM components at the apical side of the cell without primarily affecting the distribution of apical and basolateral polarity proteins. In addition, PIP2 controls the apical and lateral localization of Crag (Calmodulin-binding protein related to a Rab3 GDP/GTP exchange protein), a factor specifically required to prevent aberrant apical secretion of BM. We propose that PIP2, through the control of Crag's subcellular localization, restricts the secretion of BM proteins to the basal side.
    Proceedings of the National Academy of Sciences 05/2014; · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The organization of cells into interconnected structures such as animal tissues requires a sophisticated system directing receptors and adhesion proteins to the cell surface. The Rab11 small G proteins (Rab11a, b, and Rab25) of the Ras superfamily are master regulators of the surface expression of receptors and adhesion proteins. Acting as a molecular switch, Rab11 builds distinct molecular machinery such as motor protein complexes and the exocyst to transport proteins to the cell surface. Recent evidence reveals Rab11 localization at the trans-Golgi network (TGN), post-Golgi vesicles, and the recycling endosome, placing it at the intersection between the endocytic and exocytic trafficking pathways. We review Rab11 in various cellular contexts, and discuss its regulation and mechanisms by which Rab11 couples with effector proteins.
    Trends in cell biology 03/2014; · 12.12 Impact Factor

Full-text (2 Sources)

Download
16 Downloads
Available from
Jun 1, 2014