DIAPH1

Cilia effects upon perturbation of DIAPH1

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Overexpression effect:

longer cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect 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:

abnormal vertebral arch morphology, abnormal vertebrae morphology

Human ciliopathy phenotype:

progressive microcephaly-seizures-cortical blindness-developmental delay syndrome; autosomal dominant nonsyndromic hearing loss 1

Subcellular localization

cilia, microtubules

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Transcription regulation
• Cilia length regulation

Function

Promotes both actin polymerization and EB1- dependent microtubule (MT) stability, both actin nucleating and microtubule-stabilizing properties of DIAPH1 are important for their cilia functions. Depletion of DIAPH1 decreased ciliogenesis, cilia length, and reduced trafficking within cilia. Conversely, targeting of DIAPH1 specifically to the basal body causes an increase in cilia length and increased trafficking within cilia. Thought to regulate cilia mainte nce in part by regulating vesicular trafficking to the base of the primary cilia (33124112). Using siRNA-mediated depletion of DIAPH1, we observed impaired ciliogenesis and reduced cilia length.