کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10954196 | 1097846 | 2010 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HAX-1: A multifaceted antiapoptotic protein localizing in the mitochondria and the sarcoplasmic reticulum of striated muscle cells
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
HAX-1 comprises a family of ubiquitously expressed proteins with antiapoptotic properties. In the current study, we investigated HAX-1's temporospatial distribution in rat striated muscles during development and in adulthood. In cardiocytes, HAX-1 is organized at the level of Z-disks throughout embryogenesis and adulthood; however, in skeletal myofibers, it is in register with M-bands during embryonic and early postnatal life and Z-disks during late postnatal and adult life. Immunoelectron microscopy and subcellular fractionation demonstrated that HAX-1 proteins localize at the mitochondrial and sarcoplasmic reticulum (SR) membranes, as well as at sites where the two are closely apposed. Variants I and II selectively concentrate in the mitochondrial membranes, whereas variants III, IV, and V localize in both organelles, albeit to varying extents. Deletion analysis combined with cellular transfections indicated that elimination of HAX-1's NH2-terminus abolishes its mitochondrial targeting and attenuates its antiapoptotic capacity, while removal of its binding site for the SR protein phospholamban (PLN) prevents its translocation to the SR. Consistent with this, HAX-1 is preferentially lost from the SR of PLN-deficient hearts. Our findings are the first to present a comprehensive characterization of HAX-1's expression in striated muscles and to provide insights on the mechanisms through which it may modulate apoptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 48, Issue 6, June 2010, Pages 1266-1279
Journal: Journal of Molecular and Cellular Cardiology - Volume 48, Issue 6, June 2010, Pages 1266-1279
نویسندگان
Solomon V. Yap, Elizabeth Vafiadaki, John Strong, Aikaterini Kontrogianni-Konstantopoulos,