MTOR

Cilia effects upon perturbation of MTOR

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Shorter cilia

Overexpression effect:

Unknown

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.43) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

preweaning lethality, complete penetrance, increased circulating sodium level, decreased blood urea nitrogen level

Human ciliopathy phenotype:

Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome; clear cell renal carcinoma; Intellectual disability

Ciliopathy associations

• Medulloblastoma
• Nephronophthisis

Subcellular localization

cilia associated gene, cytosol, endosome, nucleus, ribosome

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Metabolism
• T cell biology
• Neurogenesis & migration
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Cardiac & muscle development
• Muscle contraction & physiology
• Cilia length regulation

Function

Mutations in MTOR Disrupt Neuro l Ciliogenesis and decreases cilia length, via induction of aberrant accumulation of OFD1 at centriolar satellites ( 29937275). Downregulated by cilium bending, which in turn regulates cell size ( 21145495). Inhibition of mTOR induces primary cilia formation, mTOR inhibition leads to the activation of autophagy, which suppresses the proteasome and prevents the degradation of ciliary proteins resulting in ciliogenesis ( 32213867, 29180513, 25906314). Involved in the elongation and mainte nce of cilium size by promoting the biosynthesis of proteins and lipids required for cilium elongation and mainte nce ( 29180513).

Model organism evidence