共 59 条
TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia
被引:302
作者:
Mukhopadhyay, Saikat
[1
]
Wen, Xiaohui
[2
]
Chih, Ben
[2
]
Nelson, Christopher D.
[3
]
Lane, William S.
[4
]
Scales, Suzie J.
[2
]
Jackson, Peter K.
[1
]
机构:
[1] Genentech Inc, Dept Cell Regulat, San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA
[3] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA
[4] Harvard Univ, Mass Spectrometry & Prote Resource Lab, FAS Ctr Syst Biol, Cambridge, MA 02138 USA
关键词:
G protein-coupled receptor;
TULP3;
hedgehog;
intraflagellar transport;
primary cilia;
RETROGRADE INTRAFLAGELLAR TRANSPORT;
MELANIN-CONCENTRATING HORMONE;
BIEDL-SYNDROME PROTEINS;
CAENORHABDITIS-ELEGANS;
RETINAL DEGENERATION;
FUNCTIONAL-ANALYSIS;
TUBBY PROTEINS;
NEURONAL CILIA;
CHLAMYDOMONAS;
PARTICLES;
D O I:
10.1101/gad.1966210
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
Primary cilia function as a sensory signaling compartment in processes ranging from mammalian Hedgehog signaling to neuronal control of obesity. Intraflagellar transport (IFT) is an ancient, conserved mechanism required to assemble cilia and for trafficking within cilia. The link between IFT, sensory signaling, and obesity is not clearly defined, but some novel monogenic obesity disorders may be linked to ciliary defects. The tubby mouse, which presents with adult-onset obesity, arises from mutation in the Tub gene. The tubby-like proteins comprise a related family of poorly understood proteins with roles in neural development and function. We find that specific Tubby family proteins, notably Tubby-like protein 3 (TULP3), bind to the IFT-A complex. IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. Both IFT-A and membrane phosphoinositide-binding properties of TULP3 are required for ciliary GPCR localization. TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo, and the TULP3-IFT-A interaction suggests how these proteins cooperate during neural tube patterning.
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页码:2180 / 2193
页数:14
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