کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5938608 1573460 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regular ArticlesA Mutation in Rab38 Small GTPase Causes Abnormal Lung Surfactant Homeostasis and Aberrant Alveolar Structure in Mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Regular ArticlesA Mutation in Rab38 Small GTPase Causes Abnormal Lung Surfactant Homeostasis and Aberrant Alveolar Structure in Mice
چکیده انگلیسی

The chocolate mutation, which is associated with oculocutaneous albinism in mice, has been attributed to a G146T transversion in the conserved GTP/GDP-interacting domain of Rab38, a small GTPase that regulates intracellular vesicular trafficking. Rab38 displays a unique tissue-specific expression pattern with highest levels present in the lung. The purpose of this study was to characterize the effects of Rab38-G146T on lung phenotype and to investigate the molecular basis of the mutant gene product (Rab38cht protein). Chocolate lungs exhibited a uniform enlargement of the distal airspaces with mild alveolar destruction as well as a slight increase in lung compliance. Alveolar type II cells were engorged with lamellar bodies of increased size and number. Hydrophobic surfactant constituents (ie, phosphatidylcholine and surfactant protein B) were increased in lung tissues but decreased in alveolar spaces, consistent with a malfunction in lamellar body secretion and the subsequent cellular accumulation of these organelles. In contrast to wild-type Rab38, native Rab38cht proteins were found to be hydrophilic and not bound to intracellular membranes. Unexpectedly, recombinant Rab38cht proteins retained GTP-binding activity but failed to undergo prenyl modification that is required for membrane-binding activity. These results suggest that the genetic abnormality of Rab38 affects multiple lysosome-related organelles, resulting in lung disease in addition to oculocutaneous albinism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 173, Issue 5, November 2008, Pages 1265-1274
نویسندگان
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