8S7C

Ternary Complex of Cachd1, FZD5 and LRP6

Summary for 8S7C

• Entry DOI: 10.2210/pdb8s7c/pdb
• Descriptor: VWFA and cache domain-containing protein 1, Frizzled-5, Low-density lipoprotein receptor-related protein 6, ... (5 entities in total)
• Functional Keywords: cachd1 frizzled-5 lrp6, signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 9
• Total formula weight: 637942.28

Authors

Zhao, Y.,Ren, J.,Jones, E.Y. (deposition date: 2024-02-29, release date: 2024-04-24, Last modification date: 2024-10-16)

Primary citation

Powell, G.T.,Faro, A.,Zhao, Y.,Stickney, H.,Novellasdemunt, L.,Henriques, P.,Gestri, G.,Redhouse White, E.,Ren, J.,Lu, W.,Young, R.M.,Hawkins, T.A.,Cavodeassi, F.,Schwarz, Q.,Dreosti, E.,Raible, D.W.,Li, V.S.W.,Wright, G.J.,Jones, E.Y.,Wilson, S.W.
Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.
Science, 384:573-579, 2024

PubMed Abstract: Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain.

PubMed: 38696577
DOI: 10.1126/science.ade6970

Experimental method

X-RAY DIFFRACTION (4.7 Å)