GPBAR1

Cilia effects upon perturbation of GPBAR1

Ciliogenesis screen results (4 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.70) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (robust z=2.30, ciliated=55.2%) PMID:26595381

Phenotypes

Mouse phenotype:

abnormal lymph node morphology

Mouse ciliopathy phenotype:

increased circulating alanine transamise level, abnormal kidney morphology, small testis, abnormal testis morphology

Subcellular localization

cilia

Functional category

• Ciliary assembly/disassembly
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Also known as TGR5. Linked to ERK sig ling, which is activated in ciliated cholangiocytes but inhibited in nonciliated cholangiocytes. Involved in bile acid-induced proliferation of nonciliated cells. Its localisation allows cholangiocyte functio l responses to bile acid sig ling(39572588). TGR5 is a bile acid receptor (GPCR) expressed in cholangiocytes and localized to several cellular compartments, especially the apical membrane, primary cilium, and nucleus. Its function depends strongly on whether the cell has a primary cilium. When activated, TGR5 produces opposite signaling effects in ciliated versus nonciliated cells: in nonciliated cells, it increases cAMP and cell proliferation via Gαs signaling, while in ciliated cells, it decreases cAMP, activates ERK signaling, and inhibits proliferation via Gαi signaling. These differences highlight that ciliary localization of TGR5 is critical in determining cellular responses to bile acids and may play an important role in cilia-related liver diseases such as polycystic liver disease(PMID: 23578785).