Year: 2023
Type: article
Abstract: Tip links are seen under microscopes as double-helical tetrameric complexes of long nonclassical cadherins, cadherin-23 and protocadherin-15. The twisted filamentous structure enables tip links to regulate mechanotransduction in hearing and balance. While the molecular details of the double-helical protocadherin-15 cis dimers have been deciphered, a similar conformation of cadherin-23 is still elusive. In a search of cadherin-23 cis dimers, we performed photoinduced cross-linking of unmodified proteins in solution and on lipid membranes and observed no trace of cadherin-23 cis dimers. Reportedly, tip links are dynamic connections, assembling and disassembling in seconds. Using lipid vesicles, we measured significantly slower aggregations between cis dimers of tip link cadherins than via dimer–monomer interactions, indicating that the trans interactions between two cis dimers may possess steric restraints and defer reassociations. Reconnections of tip links are thus kinetically most desired between protocadherin-15 cis dimers and cadherin-23 monomers. Here we propose that the helical geometry of tip links is induced by protocadherin-15 cis dimers, while cadherin-23 remains single before tip linking.
Source: Biochemistry
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Indian Institute of Science, Wellcome Trust, Department of Biotechnology, Ministry of Science and Technology, India, The Wellcome Trust DBT India Alliance, Indian Institute of Science Education and Research Mohali, Science and Engineering Research Board, National Centre for Biological Sciences
OpenAlex ID: W4382989005