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Gene Review:

CRB3 - crumbs family member 3

Homo sapiens

Synonyms: MGC17303, Protein crumbs homolog 3, UNQ588/PRO1158

Lemmers, C. et al., Massey-Harroche, D. et al., Michel, D. et al., Makarova, O. et al., Taricani, L. et al., et al.

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High impact information on CRB3

Here we report, using a two-hybrid assay, a direct molecular interaction between TSC2 C-terminal part and PDZ 2 and 3 of PATJ, a scaffold member of the Crumbs 3 (CRB 3) complex in human intestinal epithelial cells, Caco2 [1].
Genetic and biochemical analyses suggest that Crb3 has a role in the maintenance of DNA damage checkpoint and influences the Rad4TopBP1 damage checkpoint function [2].
RESULTS: Here we show that CRB3, a CRB1-related protein found in epithelia, is localized to cilia and required for proper cilia formation [3].
Indeed, expression of CRB3 or of a chimera containing the extracellular domain of the neurotrophin receptor p75NTR and the transmembrane and cytoplasmic domains of CRB3 led to a slower development of functional tight junctions in Madin-Darby canine kidney cells [4].
CRB3 is localized to the apical and subapical area of epithelial cells from the mouse and human intestine, suggesting that it could play a role in epithelial morphogenesis [4].

Biological context of CRB3

Thus, CRB3, through its cytoplasmic domain and its interactors, plays a role in apical membrane morphogenesis and tight junction regulation [4].
This phenotype relied on the presence of CRB3 four last amino acids (ERLI) that are involved in a direct interaction with Par6, a regulator of epithelial polarity and tight junction formation [4].

Anatomical context of CRB3

CRB3 is localized to the apical surface and tight junctions but the conserved N linked glycosylation site does not appear to be necessary for CRB3 apical targeting [5].
We also identified a partial cDNA coding the transmembrane and cytoplasmic domains of a new human crumbs (CRB3) expressed in Caco-2 cells [6].

Physical interactions of CRB3

Thus, PATJ stabilizes the Crb3 complex and regulates the spatial concentration of several components at the border between the apical and lateral domains [7].

Other interactions of CRB3

In the current report we have cloned a full length cDNA for a human paralogue of CRB1 called Crumbs3 (CRB3) [5].

References

Evidence for a molecular link between the tuberous sclerosis complex and the Crumbs complex. Massey-Harroche, D., Delgrossi, M.H., Lane-Guermonprez, L., Arsanto, J.P., Borg, J.P., Billaud, M., Le Bivic, A. Hum. Mol. Genet. (2007) [Pubmed]
Rad4TopBP1, a scaffold protein, plays separate roles in DNA damage and replication checkpoints and DNA replication. Taricani, L., Wang, T.S. Mol. Biol. Cell (2006) [Pubmed]
Polarity proteins control ciliogenesis via kinesin motor interactions. Fan, S., Hurd, T.W., Liu, C.J., Straight, S.W., Weimbs, T., Hurd, E.A., Domino, S.E., Margolis, B. Curr. Biol. (2004) [Pubmed]
CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. Lemmers, C., Michel, D., Lane-Guermonprez, L., Delgrossi, M.H., Médina, E., Arsanto, J.P., Le Bivic, A. Mol. Biol. Cell (2004) [Pubmed]
Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1). Makarova, O., Roh, M.H., Liu, C.J., Laurinec, S., Margolis, B. Gene (2003) [Pubmed]
hINADl/PATJ, a homolog of discs lost, interacts with crumbs and localizes to tight junctions in human epithelial cells. Lemmers, C., Médina, E., Delgrossi, M.H., Michel, D., Arsanto, J.P., Le Bivic, A. J. Biol. Chem. (2002) [Pubmed]
PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells. Michel, D., Arsanto, J.P., Massey-Harroche, D., Béclin, C., Wijnholds, J., Le Bivic, A. J. Cell. Sci. (2005) [Pubmed]

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