HYLS1

Cilia effects upon perturbation of HYLS1

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Impaired ciliogenesis

Ciliogenesis screen results (1 screen)

• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

abnormal heart looping, embryonic growth retardation, preweaning lethality, complete penetrance, decreased prepulse inhibition, abnormal embryo size, pretal lethality prior to heart atrial septation, prolonged pq interval, long tibia

Mouse ciliopathy phenotype:

abnormal embryo turning

Human ciliopathy phenotype:

Joubert syndrome; severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome

Ciliopathy associations

• Hydrolethalus Syndrome
• Joubert Syndrome

Subcellular localization

basal body, centrosome, cilia, nucleus

Functional category

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

Function

Required for intraflagellar transport trafficking and for centrioles to form cilia. Loss of HYLS-1 results in severe defects in axoneme assembly and transition zone organisation, due to impaired entry of IFT machinery to the cilia via DYF-19 (28411189). Ciliogenesis mediation by regulating the formation of the ciliary gate, minor role in transition zone assembly. Required for distal centriole elongation and recruiting distal centriole proteins (32509774). Essential for the apical targeting and/or anchoring of centrioles/basal body at the plasma membrane, contributin to basal body organisation (19656802). Loss of HYLS1 inhibits ciliogenesis. RCTE cells treated with HYLS1 siRNAs— percentage of ciliated cells and the length of cilium were quantified. (34162535) HYLS-1 acts as a centriolar scaffold for cilia assembly … HYLS-1 is required for mother centriole to acquire the capacity to form cilia.(19656802) Loss of HYLS-1 compromises the docking and entry of intraflagellar transport particles, ciliary gating for both membrane and soluble proteins, and axoneme assembly. (27534274) HYLS1 and TUBB promote centriole triplet microtubule assembly. HYLS1 ciliopathy-related residue D211 physically traps the wobbling C-terminal tail of TUBB, suppressing its inhibitory role in incomplete microtubule assembly initiation.

Model organism evidence