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XB-ART-49380
Dev Biol October 1, 2014; 394 (1): 54-64.

Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric kidney by modulating lipid rafts.

Cerqueira DM , Tran U , Romaker D , Abreu JG , Wessely O .


Abstract
The kidney is a homeostatic organ required for waste excretion and reabsorption of water, salts and other macromolecules. To this end, a complex series of developmental steps ensures the formation of a correctly patterned and properly proportioned organ. While previous studies have mainly focused on the individual signaling pathways, the formation of higher order receptor complexes in lipid rafts is an equally important aspect. These membrane platforms are characterized by differences in local lipid and protein compositions. Indeed, the cells in the Xenopus pronephric kidney were positive for the lipid raft markers ganglioside GM1 and Caveolin-1. To specifically interfere with lipid raft function in vivo, we focused on the Sterol Carrier Protein 2 (scp2), a multifunctional protein that is an important player in remodeling lipid raft composition. In Xenopus, scp2 mRNA was strongly expressed in differentiated epithelial structures of the pronephric kidney. Knockdown of scp2 did not interfere with the patterning of the kidney along its proximo-distal axis, but dramatically decreased the size of the kidney, in particular the proximal tubules. This phenotype was accompanied by a reduction of lipid rafts, but was independent of the peroxisomal or transcriptional activities of scp2. Finally, disrupting lipid micro-domains by inhibiting cholesterol synthesis using Mevinolin phenocopied the defects seen in scp2 morphants. Together these data underscore the importance for localized signaling platforms in the proper formation of the Xenopus kidney.

PubMed ID: 25127994
PMC ID: PMC4163507
Article link: Dev Biol
Grant support: [+]
Genes referenced: abcd3 atp1b1 bsg cat.1 cat.2 cav1 cltc lta nphs1 psmd6 rab5a rab7a scp2 slc12a1 slc12a3 slc5a9 slc7a5
GO keywords: kidney development
Antibodies: Kidney Ab1 Kidney Ab2 cav1 Ab1 cltc Ab1 rab5a Ab1 rab7a Ab1
Morpholinos: scp2 MO1 scp2 MO2


Article Images: [+] show captions
References [+] :
Adams, Inverse drug screens: a rapid and inexpensive method for implicating molecular targets. 2006, Pubmed


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