LRRC45

Cilia effects upon perturbation of LRRC45

Cilia number / % ciliated:

Decrease

Loss-of-function effect:

Decrease

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Increased Signaling (Negative Regulator) PMID:29459680

Phenotypes

Human ciliopathy phenotype:

Severe central nervous system anomalies, pontocerebellar hypoplasia, neural migration defects, neurodevelopmental disorder (3 individuals, 2 families; biallelic LRRC45 variants)

Ciliopathy associations

• Intellectual Developmental Disorder

Subcellular localization

distal appendage, proximal centriole, transition zone

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Transition zone

Function

Recruits the keratin-binding protein FBF1. Promotes cilia biogenesis in CP110- uncapped centrioles by organising centriolar satellites. It is required for centrosome cohesion at the proximal end of centrioles. Establishes the transition zone, recruitment of Rab8 and satellites to centrosomes, and promotes the docking of Rab8 GTPase-positive vesicles to the mother centriole (30131441). P1 fibroblasts showed a significant reduction of primary cilia frequency and length. (39638757) Loss of LRRC45 led to a reduction of cilia formation in serum-starved RPE1 cells … primary cilia in LRRC45 depleted cells were shorter in comparison to control depleted cells. (30131441) Biallelic LRRC45 variants cause severe neurological ciliopathy. Patient fibroblasts show significant reduction of primary cilia frequency and length. LRRC45 is essential for transition zone establishment and axonemal extension during early ciliogenesis.