Files and links (2)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Ceramide Kinase-Like (CERKL) Interacts with Neuronal Calcium Sensor Proteins in the Retina in a Cation-Dependent Manner
Investigative ophthalmology & visual science, v 53(8), pp 4565-4574
10 Jul 2012
PMID: 22678504
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
PURPOSE. CERKL encodes for a ceramide kinase (CERK)-like protein. CERKL mutations are associated with severe retinal degeneration. Several studies have been conducted to prove a biochemical similarity between CERK and CERKL enzymatic activities. However, so far there has been no evidence that CERKL phosphorylates ceramide or any other lipid substrate in vitro or in vivo. The purpose of this work was to characterize CERKL's function by identification of CERKL-interacting proteins in the mammalian retina.
METHODS. CERKL-interacting proteins were identified implementing the Ras-recruitment system (RRS) on a bovine retina cDNA library. Co-immunoprecipitation (co-IP) in transfected cells and in photoreceptor outer segments was used to verify the identified interactions. Serial deletion constructs were used to map the interacting sites. CERKL's kinase activity was tested by a CERK activity assay.
RESULTS. We identified an interaction between CERKL and several neuronal calcium sensor (NCS) proteins, including guanylate cyclase activating protein 1 (GCAP1), GCAP2, and recoverin. These interactions were confirmed by co-IP experiments in transfected mammalian cells. Moreover, the interaction between endogenous CERKL and GCAP2 was confirmed by co-IP in photoreceptor outer segments. We found that CERKL-GCAP interaction is cation dependent and is mediated by CERKL's N-terminal region and by GCAPs cation-binding domains (EF-hands 2-4).
CONCLUSIONS. This study, which is the first to describe the interactions of CERKL with other retinal proteins, links CERKL to proteins involved in the photoresponse and Ca2+ signaling, providing important clues for future research required in this direction. (Invest Ophthalmol Vis Sci. 2012;53:4565-4574) DOI: 10.1167/iovs.12-9770
Metrics
Details
- Title
- Ceramide Kinase-Like (CERKL) Interacts with Neuronal Calcium Sensor Proteins in the Retina in a Cation-Dependent Manner
- Creators
- Mariela J. Nevet - Technion – Israel Institute of TechnologySharon Vekslin - Rappaport Family Institute for Research in the Medical SciencesAlexander M. Dizhoor - Salus UniversityElena V. Olshevskaya - Salus UniversityRotem Tidhar - Weizmann Institute of ScienceAnthony H. Futerman - Weizmann Institute of ScienceTamar Ben-Yosef - Rappaport Family Institute for Research in the Medical Sciences
- Publication Details
- Investigative ophthalmology & visual science, v 53(8), pp 4565-4574
- Publisher
- Assoc Research Vision Ophthalmology Inc
- Number of pages
- 10
- Grant note
- R01EY011522 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) EY11522 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 567/09 / Israel Science Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000307096400030
- Scopus ID
- 2-s2.0-84866497961
- Other Identifier
- 991022035114204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Ophthalmology