MAEA

Cilia effects upon perturbation of MAEA

Ciliogenesis screen results (4 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (z=2.53) 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:

abnormal coat appearance; preweaning lethality; complete penetrance

Subcellular localization

cilia associated gene, cytosol, nucleoplasm

Functional category

• Signaling (Hedgehog, GPCRs, ion channels)

Function

Starting from 147 Ub-related components with connections to cilia or Hedgehog signaling, we identified 40 genes whose loss altered Hedgehog signaling as measured by a Gli-GFP reporter. 9 of these 40 caused aberrant Smo accumulation in cilia at the basal state. The nine included an E2-conjugating enzyme (Ube2l3), four E3 ligases (Wwp1, Arih2, Mgrn1, and Maea), a deubiquitinating enzyme (DUB; Bap1), and three adaptors (Kctd5, Skp1a, and Skp2). The E3 ligases appear to function in discrete steps where Arih2 regulates cellular levels of Smo, Wwp1 regulates ciliary levels directly, and Mgrn1 and Maea function in the cytoplasm. Our findings shed light on the long-standing enigma of how the ciliary levels of Smo are regulated by Hedgehog signaling E3 ligase; LoF causes Smo accumulation in cilia at basal state (PMID: 34161574).