PUBLICATION
Members of the vertebrate contactin and amyloid precursor protein families interact through a conserved interface
- Authors
- Karuppan, S.J., Vogt, A., Fischer, Z., Ladutska, A., Swiastyn, J., McGraw, H.F., Bouyain, S.
- ID
- ZDB-PUB-211230-42
- Date
- 2021
- Source
- The Journal of biological chemistry 298(2): 101541 (Journal)
- Registered Authors
- Keywords
- X‐ray crystallography, amyloid precursor protein (APP), axon, cell adhesion, cell surface protein, contactin, protein‐protein interaction, zebrafish
- MeSH Terms
-
- Amyloid beta-Peptides*/metabolism
- Amyloid beta-Protein Precursor*/metabolism
- Animals
- Axons/metabolism
- Contactins/metabolism
- Zebrafish/metabolism
- PubMed
- 34958801 Full text @ J. Biol. Chem.
Citation
Karuppan, S.J., Vogt, A., Fischer, Z., Ladutska, A., Swiastyn, J., McGraw, H.F., Bouyain, S. (2021) Members of the vertebrate contactin and amyloid precursor protein families interact through a conserved interface. The Journal of biological chemistry. 298(2):101541.
Abstract
Contactins (CNTN) are neural cell adhesion molecules that encode axon-target specificity during the patterning of the vertebrate visual and olfactory systems. Because CNTNs are tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, they lack an intracellular region to communicate across the membrane. Instead, they form co-receptor complexes with distinct transmembrane proteins to transmit signals inside the cell. In particular, a complex of CNTN4 and amyloid precursor protein (APP) is known to guide the assembly of specific circuits in the visual system. Here, using in situ hybridization in zebrafish embryos, we show that CNTN4, CNTN5, and the APP homologues APLP1 and APLP2 are expressed in olfactory pits, suggesting that these receptors may also function together in the organization of olfactory tissues. Furthermore, we use biochemical and structural approaches to characterize interactions between members of these two receptor families. In particular, APP and APLP1 interact with CNTN3-5, while APLP2 only binds to CNTN4 and 5. Finally, structural analyses of five CNTN/amyloid pairs indicate that these proteins interact through a conserved interface involving the second fibronectin type III repeat of CNTNs and the copper-binding domain of amyloid proteins. Overall, this work sets the stage for analyzing CNTN/amyloid-mediated connectivity in vertebrate sensory circuits.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping