PKHD1L1

Cilia effects upon perturbation of PKHD1L1

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.75) 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, increased red blood cell distribution width, increased monocyte cell number, decreased lymphocyte cell number

Human ciliopathy phenotype:

autosomal recessive nonsyndromic hearing loss 124

Ciliopathy associations

• Nonsyndromic Tetralogy of Fallot

Subcellular localization

basal body, cytosol, flagella, lysosomes

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation

Function

PKHD1L1 has localized in basal body,flagella. We first examined the subcellular localization of these ciliary genes in both mouse embryonic fibroblasts (MEFs) and E10.5 mouse OFTs. Immunofluorescence staining analysis revealed that Mlf1 and Pkhd1l1 colocalized with acetylated α-tubulin and specifically accumulated in cilia axonemes, Sptbn5 colocalized with both acetylated α-tubulin and γ-tubulin along the entire cilia, Ppef2 and Tekt3 were localized to basal bodies of cilia, and Agbl2 was located at the base of cilia and overlapped with Nek2, a marker of centriole (Fig. 5A and fig. S16). ). Ultrastructural analysis using TEM further revealed that Pkhd1l1−/− mouse OFT tissues displayed severely disorganized ciliary axonemes, with microtubule loss and irregular ciliary distribution and orientation, compared to the typical 9+0 microtubule arrangement in wild-type Pkhd1l1+/+ mice (Fig. 3, I and J). Thus, these findings highlight the critical role of ciliary genes in ciliogenesis and their essential function located in cardiac OFT development. (41071877)