RER1

Cilia effects upon perturbation of RER1

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-8.49) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Increased Signaling (Negative Regulator) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

decreased thigmotaxis, hyperactivity, abnormal behavior, decreased bone mineral content, abnormal bone structure, embryonic lethality prior to organogenesis, preweaning lethality, complete penetrance

Subcellular localization

cilia associated gene, endoplasmic reticulum, golgi apparatus

Functional category

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

Function

We identified Rer1p as the first endoplasmic reticulum/cis-Golgi-localized membrane protein involved in ciliogenesis. Rer1p, a protein quality control receptor, was highly expressed in zebrafish ciliated organs and regulated ciliary structure and function. Both in zebrafish and mammalian cells, loss of Rer1p resulted in the shortening of cilium and impairment of its motile or sensory function, which was reflected by hearing, vision, and left-right asymmetry defects as well as decreased Hedgehog signaling. We further demonstrate that Rer1p depletion reduced ciliary length and function by increasing γ-secretase complex assembly and activity and, consequently, enhancing Notch signaling as well as reducing Foxj1a expression(23479743).

Model organism evidence