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Affinity Requirements For Control Of Synaptic Targeting And Neuronal Cell Survival By Heterophilic IgSF Cell Adhesion Molecules

Xu, Shuwa and Sergeeva, Alina P. and Katsamba, Phinikoula S. and Mannepalli, Seetha and Bahna, Fabiana and Bimela, Jude and Zipursky, Lawrence S. and Shapiro, Lawrence and Honig, Barry and Zinn, Kai (2021) Affinity Requirements For Control Of Synaptic Targeting And Neuronal Cell Survival By Heterophilic IgSF Cell Adhesion Molecules. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210218-144331878

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Abstract

Neurons in the developing brain express many different cell adhesion molecules (CAMs) on their surfaces, and CAM interactions are essential for the determination of synaptic connectivity patterns. CAM binding affinities can vary by more than 200-fold, but the significance of affinity differences among CAMs is unknown. Here we provide a systematic characterization of the in vivo consequences of altering CAM affinity. Interactions between DIP-α and its binding partners Dpr6 and Dpr10 control synaptic targeting and cell survival for Drosophila optic lobe neurons. We generated mutations that change DIP-α::Dpr10 binding affinity and introduced these into the endogenous loci. We show that cell survival and synaptic targeting have different affinity requirements, and that there is a threshold affinity required for targeting. Reducing affinity causes graded loss-of-function phenotypes, while increasing affinity rescues cells that would normally die. Affinity reduction can be compensated for by increasing gene copy number.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.02.16.431482DOIDiscussion Paper
ORCID:
AuthorORCID
Zinn, Kai0000-0002-6706-5605
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. This version posted February 17, 2021. We would like to thank Richard Mann, Kaushiki Menon and Namrata Bali for general discussions. Confocal imaging was completed in the Caltech Biological Imaging Facility. This work was supported by Kai Zinn’s NIH grants R37 NS028182 and RO1 NSN096509; and Barry Honig’s NSF grant MCB-1914542. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
NIHR37 NS028182
NIHRO1 NSN096509
NSFMCB-1914542
Record Number:CaltechAUTHORS:20210218-144331878
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210218-144331878
Official Citation:Affinity Requirements For Control Of Synaptic Targeting And Neuronal Cell Survival By Heterophilic IgSF Cell Adhesion Molecules. Shuwa Xu, Alina P Sergeeva, Phinikoula S. Katsamba, Seetha Mannepalli, Fabiana Bahna, Jude Bimela, Lawrence S. Zipursky, Lawrence Shapiro, Barry Honig, Kai Zinn. bioRxiv 2021.02.16.431482; doi: https://doi.org/10.1101/2021.02.16.431482
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108106
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Feb 2021 23:37
Last Modified:18 Feb 2021 23:37

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