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PMID:23063435

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Citation

'Peschard, P, McCarthy, A, Leblanc-Dominguez, V, Yeo, M, Guichard, S, Stamp, G and Marshall, CJ (2012) Genetic Deletion of RALA and RALB Small GTPases Reveals Redundant Functions in Development and Tumorigenesis. Curr. Biol. '

Abstract

RAL small GTPases, encoded by the Rala and Ralb genes, are members of the RAS superfamily of small GTPases and can act as downstream effectors of RAS [1]. Although highly similar, distinct functions have been identified for RALA and RALB: RALA has been implicated in epithelial cell polarity [2], insulin secretion [3], GLUT4 translocation [4, 5], neurite branching, and neuronal polarity [6, 7], and RALB in tumor cell survival [8], migration/invasion [9-12], TBK1 activation [13], and autophagy [14]. To investigate RAL GTPases in vivo, we generated null and conditional knockout mice. Ralb null mice are viable with no overt phenotype; the Rala null leads to exencephaly and embryonic lethality. The exencephaly phenotype is exacerbated in Rala(-/-);Ralb(+/-) embryos; embryos null for Rala and Ralb do not live past gastrulation. Using a Kras-driven non-small cell lung carcinoma mouse model, we found that either RALA or RALB is sufficient for tumor growth. However, deletion of both Ral genes blocks tumor formation. Either RALA or RALB is sufficient for cell proliferation, but cells lacking both fail to proliferate. These studies demonstrate functions of RAL proteins in development, tumorigenesis, and cell proliferation and show that RALA and RALB act in a redundant fashion.

Links

PubMed Online version:10.1016/j.cub.2012.09.013

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RALA

GO:0001843: neural tube closure

ECO:0000315:

P

Figure 1 depicts exencephaly in null Rala embryos.

complete
CACAO 5341

MOUSE:RALA

involved_in

GO:0001843: neural tube closure

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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