Abstract
BackgroundTubby is the founding member of the tubby-like family of proteins. The naturally occurring tubby mutation in mice causes retinitis pigmentosa, hearing loss and obesity. Tubby has been proposed to function as an accessory factor in ciliary trafficking. We directly examined a role for tubby in ciliary trafficking in vivo.MethodsWe used immunofluoresence labeling to examine the subcellular localization of rhodopsin, somatostatin receptor 3 (SSTR3) and melanin concentrating hormone receptor 1 (MCHR1), all of which are G protein-coupled receptors (GPCR), in the retina and brain of wild type (WT) and tubby mutant mice.ResultsIn tubby mouse retina, rhodopsin is not fully transported across the connecting cilia to the outer segments with ensuing photoreceptor degeneration. In the tubby mouse brain, SSTR3 and MCHR1 fail to localize at the neuronal primary cilia in regions where these receptors play critical roles in neural signaling. The tubby mutant does not manifest a generalized defect in ciliogenesis or protein trafficking.ConclusionsTubby plays a critical role in trafficking select GPCRs to the cilia. This role is reminiscent of tubby-like proteins 1 and 3, which have been proposed to facilitate trafficking of rhodopsin and select GPCRs in photoreceptors and the developing neural tube, respectively. Thus tubby-like proteins may be generally involved in transciliary trafficking of GPCRs.
Highlights
Tubby is the founding member of the tubby-like family of proteins
We examined the subcellular distribution of a number G protein-coupled receptors (GPCR) and show that tubby is essential for GPCR trafficking in the neuronal and sensory cilia
We have demonstrated that tubby is required for the transciliary trafficking of two GPCRs, melanin concentrating hormone receptor 1 (MCHR1) and somatostatin receptor 3 (SSTR3)
Summary
Tubby is the founding member of the tubby-like family of proteins. The naturally occurring tubby mutation in mice causes retinitis pigmentosa, hearing loss and obesity. The tubby-like proteins are defined by a highly conserved carboxyl terminal half of their primary sequence known as the tubby signature domain [1,2]. This family of proteins includes the prototype tubby, and TULP1, 2 and 3, for tubby-like proteins 1, 2 and 3 [3,4,5]. TULP3 facilitates membrane receptor trafficking to primary cilia It serves as bipartite bridges through their phosphoinositide-binding tubby domain and N-terminal IFT-binding motif, coordinating multiple signaling pathways including membrane receptor trafficking [15]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.