title: The molecular interaction of heart LIM protein (HLP) with RyR2 and caveolin-3 is essential for Ca(2+)-induced Ca(2+) release in the heart.
abstract: The heart LIM protein (HLP) is a LIM-only protein family member that mediates protein-protein interactions. To date, no studies have yet been conducted regarding its function in the heart. In the present study, we have identified that HLP binds the cytosolic region of RyR2 in the heart using a bacterial two-hybrid system, LC-MS/MS, co-immunoprecipitation, and GST-pull down assays. Microscopy revealed that HLP forms a triple complex with RyR2 and caveolin-3. siRNA and adenovirus-mediated KD of HLP decreased the electrically evoked Ca(2+) release from the sarcoplasmic reticulum without directly affecting SERCA2 and RyR2 activities. Collectively, the HLP-RyR2 interaction in the cell surface caveolae region may be essential for efficient excitation-contraction coupling in the heart.
authors.affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Song
authors.affiliation: Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Ryu
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
authors.affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea. Electronic address: dhkim@gist.ac.kr.
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051244:Caveolin 3 / Q000378:metabolism*; D002460:Cell Line; D060588:LIM Domain Proteins / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: C495549:Cav3 protein, rat; D051244:Caveolin 3; C544610:Crip2 protein, rat; D060588:LIM Domain Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium
keywords: Ca(2+) release channel; Caveolae; Dihydropyridine receptor; Excitation-contraction coupling; LIM domain