LEPR

Cilia effects upon perturbation of LEPR

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.17) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

increased neutrophil cell number, decreased leukocyte cell number, impaired righting response, decreased locomotor activity, decreased bone mineral density, decreased bone mineral content, increased mean corpuscular volume, increased mean corpuscular hemoglobin, increased total body fat amount, tremors, increased circulating total protein level, increased circulating calcium level, increased red blood cell distribution width, increased circulating potassium level, increased circulating iron level, increased circulating fructosamine level, increased circulating cholesterol level, enlarged liver, increased hemoglobin content, increased hematocrit, abnormal gait, decreased lean body mass, trunk curl, increased circulating hdl cholesterol level, increased circulating phosphate level, thrombocytopenia, decreased lymphocyte cell number, increased anxiety-related response, decreased heart weight, decreased spleen weight, increased circulating serum albumin level, decreased exploration in new environment, abnormal locomotor behavior, increased circulating glucose level, decreased circulating triglyceride level, decreased circulating chloride level, increased circulating amylase level, small semil vesicle, abnormal bone structure, limb grasping, increased mean platelet volume, increased circulating alkaline phosphatase level, increased monocyte cell number, increased eosinophil cell number

Mouse ciliopathy phenotype:

male infertility, increased circulating aspartate transamise level, increased circulating alanine transamise level, female infertility

Human ciliopathy phenotype:

obesity due to leptin receptor gene deficiency

Subcellular localization

basal body

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• T cell biology
• Signaling (Hedgehog, GPCRs, ion channels)

Function

BBS proteins are required for leptin receptor (LepR) sig ling in the hypothalamus. BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking (19150989). Immunocytochemistry for AC3 or the basal body marker 纬-tubulin in LEPR-EGFP鈥揺xpressing cells demonstrated that LEPR-EGFP localized to the 纬-tubulin鈥搒tained basal body (Figure 3A), which indicates that the leptin sig ling machinery is a tomically linked to cilia鈥揵asal body complexes(24667636) .

Model organism evidence