APP

Cilia effects upon perturbation of APP

Loss-of-function effect:

Shorter cilia

Overexpression effect:

Shorter

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:

preweaning lethality, incomplete penetrance, decreased grip strength, increased monocyte cell number, decreased total reti thickness, increased circulating calcium level, increased neutrophil cell number, increased cornea thickness, increased blood urea nitrogen level

Subcellular localization

autophagosomes, cilia, cytosol, endosome, lysosomes, microtubules, nucleus

References: PMID:30140428, PMID:34580355

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Metabolism
• Neurogenesis & migration
• Viral interactions
• Protein processing & maturation
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Axon guidance & growth
• Transcription regulation

Function

APP localizes to primary cilia and Aβ treatment results in distorted primary cilia structure. In addition, we demonstrate that Aβ treatment interrupts canonical Shh signal transduction(30140428). APP localized in motile and non-motile (sensory) cilia in zebrafish, mouse and human samples. Zebrafish App homologues are expressed by ciliated cells and become localized at the membrane of cilia in the otic vesicle, the sal epithelium, and the brain ventricles of zebrafish embryos (345803559).