Cathepsin L participates in the production of neuropeptide Y in secretory vesicles, demonstrated by protease gene knockout and expression.
Cathepsin L participates in the production of neuropeptide Y in secretory vesicles, demonstrated by protease gene knockout and expression.
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DOI：
10.1111/j.1471-4159.2008.05408.x
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发表时间：
2008-07
影响因子：
4.7
通讯作者：
Hook V
中科院分区：
文献类型：
--
作者：
Funkelstein L;Toneff T;Hwang SR;Reinheckel T;Peters C;Hook V
Neuropeptide Y (NPY) functions as a peptide neurotransmitter and as a neuroendocrine hormone. The active NPY peptide is generated in secretory vesicles by proteolytic processing of proNPY. Novel findings from this study show that cathepsin L participates as a key proteolytic enzyme for NPY production in secretory vesicles. Notably, NPY in cathepsin L knockout (KO) mice were substantially reduced in brain and adrenal medulla by 80% and 90%, respectively. Participation of cathepsin L in producing NPY predicts their colocalization in secretory vesicles, a primary site of NPY production. Indeed, cathepsin L was colocalized with NPY in brain cortical neurons and in chromaffin cells of adrenal medulla, demonstrated by immunofluorescence confocal microscopy. Immunoelectron microscopy confirmed the localization of cathepsin L with NPY in regulated secretory vesicles of chromaffin cells. Functional studies showed that coexpression of proNPY with cathepsin L in neuroendocrine PC12 cells resulted in increased production of NPY. Furthermore, in vitro processing indicated cathepsin L processing of proNPY at paired basic residues. These findings demonstrate a role for cathepsin L in the production of NPY from its proNPY precursor. These studies demonstrate the novel biological role of cathepsin L in the production of NPY, a peptide neurotransmitter and neuroendocrine hormone.
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影响因子：
4.8
作者：
Roth, W;Deussing, J;Peters, C
通讯作者：
Peters, C
影响因子：
3.5
作者：
GAINER, H;RUSSELL, JT;LOH, YP
通讯作者：
LOH, YP
影响因子：
5.3
作者：
Allen, RG;Peng, B;Pintar, JE
通讯作者：
Pintar, JE
影响因子：
4.8
作者：
AZARYAN, AV;KRIEGER, TJ;HOOK, VYH
通讯作者：
HOOK, VYH
影响因子：
3.9
作者：
Hook, VYH;Schiller, MR;Azaryan, AV
通讯作者：
Azaryan, AV