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SLMAP overexpression in mouse heart remodels subcellular membranes involved in E‐C coupling
Author(s) -
Nader Moni,
Westendorp Bart,
Salih Maysoon,
Leenen Frans HH,
Tuana Balwant S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.386.6
Subject(s) - vacuolization , calsequestrin , calnexin , endoplasmic reticulum , subcellular localization , microbiology and biotechnology , organelle , cytoplasm , membrane protein , vesicle , immunoelectron microscopy , membrane , coupling (piping) , biology , chemistry , biochemistry , immunohistochemistry , endocrinology , ryanodine receptor , materials science , metallurgy , calreticulin , immunology
SLMAP is a tail‐anchored membrane protein implicated in regulating the excitation‐contraction (E‐C) coupling. To define further its role in cardiac function we generated transgenic (Tg) mice with SLMAP1 expression driven by the α‐MHC promoter. Gross analysis indicated no changes in structure or function as a consequence of SLMAP1 expression although genes associated with cardiac remodeling such as (ANF) were up regulated. Immunohistochemical analysis revealed that SLMAP1 targets subcellular organelles and was associated with a moderate to severe vacuolization of membrane compartments in cardiomyocytes. The changes in membrane vacuolization appeared to be related to the level of SLMAP1 protein expressed as well as age of the animals with maximal membrane disruption noted at day 30–35. High resolution microscopy revealed the presence of large membranes vesicles filled with crystalline substance, consistent with dilated sarcoplasmic reticulum. The expression of proteins involved in regulating the E‐C coupling (RyR2, caveolin3, triadin) were down regulated whereas others (calsequestrin, calnexin, BiP) were up regulated. We concluded that SLMAP is involved in subcellular remodeling of E‐C coupling components and its regulated level in cardiomyocytes is critical to ensure a proper organization of subcellular compartments. (Supported by a grant from HSFO)