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Genes Dev May 1, 2010; 24 (9): 875-80.

Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development.

Saharinen P , Helotera H , Miettinen J , Norrmen C , D'Amico G , Jeltsch M , Langenberg T , Vandevelde W , Ny A , Dewerchin M , Carmeliet P , Alitalo K .

The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that clp24 knockdown in Danio rerio and Xenopus laevis results in defective lymphatic development. Targeted disruption of Clp24 in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the Clp24(-/-) phenotype was further aggravated in the Vegfr2(+/LacZ) or Vegfr3(+/LacZ) backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.

PubMed ID: 20439428
PMC ID: PMC2861186
Article link: Genes Dev

Species referenced: Xenopus laevis
Genes referenced: aplnr creb1 flt4 kdr prox1 tbx2 tmem204 tp53
GO keywords: lymphangiogenesis
Morpholinos: tmem204 MO1

Article Images: [+] show captions
References [+] :
Adams, Molecular regulation of angiogenesis and lymphangiogenesis. 2007, Pubmed