Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-12
Hao, Zhenhua
Feng, Yaqin
Ma, Jing
Li, Wei
Hao, Zhenhua
Wei, Lisi
Chen, Xiaowei
Zhou, Zhuan
Chen, Liangyi
Wei, Lisi
Chen, Xiaowei
Zhou, Zhuan
Chen, Liangyi
Feng, Yaqin
Du, Wen
Li, Wei
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.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-11
Yuan, Tianyi
Liu, Lin
Wei, Lisi
Zhao, Shiqun
Zheng, Xiaolu
Huang, Xiaoshuai
Xie, Lihan
Zong, Weijian
Yang, Lu
Liu, Yanmei
Chen, Liangyi
Yuan, Tianyi
Liu, Lin
Wei, Lisi
Zhao, Shiqun
Zheng, Xiaolu
Huang, Xiaoshuai
Xie, Lihan
Zong, Weijian
Yang, Lu
Abstract： Many receptor-mediated endocytic processes are mediated by constitutive budding of clathrin-coated pits (CCPs) at spatially randomized sites before slowly pinching off from the plasma membrane (60100 s). In contrast, clathrin-mediated endocytosis (CME) coupled with regulated exocytosis in excitable cells occurs at peri-exocytic sites shortly after vesicle fusion (similar to 10 s). The molecular mechanism underlying this spatiotemporal coupling remains elusive. We show that coupled endocytosis makes use of preformed CCPs, which hop to nascent fusion sites nearby following vesicle exocytosis. A dynamic cortical microtubular network, anchored at the cell surface by the cytoplasmic linker-associated protein on microtubules and the LL5 beta/ELKS complex on the plasma membrane, provides the track for CCP hopping. Local diacylglycerol gradients generated upon exocytosis guide the direction of hopping. Overall, the CCP-cytoskeleton-lipid interaction demonstrated here mediates exocytosis-coupled fast recycling of both plasma membrane and vesicular proteins, and it is required for the sustained exocytosis during repetitive stimulations.
Peer Review Status:Awaiting Review
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