Orphan G-Protein Coupled Receptor 22 Gpr22 Regulates Cilia Length and Structure in the Zebrafish Kupffer’s VesicleReportar como inadecuado




Orphan G-Protein Coupled Receptor 22 Gpr22 Regulates Cilia Length and Structure in the Zebrafish Kupffer’s Vesicle - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

GPR22 is an orphan G protein-coupled receptor GPCR. Since the ligand of the receptor is currently unknown, its biological function has not been investigated in depth. Many GPCRs and their intracellular effectors are targeted to cilia. Cilia are highly conserved eukaryotic microtubule-based organelles that protrude from the membrane of most mammalian cells. They are involved in a large variety of physiological processes and diseases. However, the details of the downstream pathways and mechanisms that maintain cilia length and structure are poorly understood. We show that morpholino knock down or overexpression of gpr22 led to defective left-right LR axis formation in the zebrafish embryo. Specifically, defective LR patterning included randomization of the left-specific lateral plate mesodermal genes LPM lefty1, lefty2, southpaw and pitx2a, resulting in randomized cardiac looping. Furthermore, gpr22 inactivation in the Kupffer’s vesicle KV alone was still able to generate the phenotype, indicating that Gpr22 mainly regulates LR asymmetry through the KV. Analysis of the KV cilia by immunofluorescence and transmission electron microscopy TEM, revealed that gpr22 knock down or overexpression resulted in changes of cilia length and structure. Further, we found that Gpr22 does not act upstream of the two cilia master regulators, Foxj1a and Rfx2. To conclude, our study characterized a novel player in the field of ciliogenesis.



Autor: Daphne Verleyen, Frank P. Luyten, Przemko Tylzanowski

Fuente: http://plos.srce.hr/



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