title: Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells.
abstract: The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky-Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs.
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100039, China.
authors: Zhenhua
authors: Z
authors: Hao
authors: Institute of Molecular Medicine and State Key Laboratory of Biomembrane Engineering, Peking University, Beijing 100871, China.
authors: Lisi
authors: L
authors: Wei
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China Department of Histology and Embryology, Shanxi Medical University, Taiyuan 030001, China.
authors: Yaqin
authors: Y
authors: Feng
authors: Institute of Molecular Medicine and State Key Laboratory of Biomembrane Engineering, Peking University, Beijing 100871, China.
authors: Xiaowei
authors: X
authors: Chen
authors: Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Wen
authors: W
authors: Du
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Jing
authors: J
authors: Ma
authors: Institute of Molecular Medicine and State Key Laboratory of Biomembrane Engineering, Peking University, Beijing 100871, China.
authors: Zhuan
authors: Z
authors: Zhou
authors: Institute of Molecular Medicine and State Key Laboratory of Biomembrane Engineering, Peking University, Beijing 100871, China.
authors: Liangyi
authors: L
authors: Chen
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China wli@genetics.ac.cn.
authors: Wei
authors: W
authors: Li
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D019439:Chromaffin Cells / Q000378:metabolism*; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D021381:Protein Transport; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D053379:Chromogranin A; D033921:Vesicular Transport Proteins; C000606739:muted protein, mouse
keywords: BLOC-1; CgA; Hermansky–Pudlak syndrome; Large dense core vesicle; Muted protein