Resting (basal) secretion of proteins is provided by the minor regulated and constitutive-like pathways and not granule exocytosis in parotid acinar cells
Resting (basal) secretion of proteins is provided by the minor regulated and constitutive-like pathways and not granule exocytosis in parotid acinar cells
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DOI：
10.1074/jbc.m100211200
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发表时间：
2001-06-22
影响因子：
4.8
通讯作者：
Castle, JD
中科院分区：
文献类型：
--
作者：
Huang, AY;Castle, AM;Castle, JD
腮腺静息分泌的唾液蛋白在进食期间通过副交感神经刺激原位维持，并被认为涉及低水平的颗粒胞吐作用。通过使用腮腺小叶从随意喂养的大鼠刺激低剂量卡巴胆碱作为一个在体外模拟静息分泌，我们推导出的分泌不涉及颗粒胞吐的排出蛋白质的组合物。相反，它来源于另外两种腺泡输出途径，组成型样（刺激非依赖性）途径和次要调节途径，其响应于低剂量的胆碱能或β-肾上腺素能激动剂（Castle，J，D，和Castle，A. M.（1996）J，Cell Sci，109，2591-2599）。体外收集的蛋白质组合物模拟从原位给予低水平刺激的腺体的插管导管收集的蛋白质组合物。沿着两条静息分泌途径的分泌运输沿着分析表明，组成型途径可能在布雷菲德菌素A敏感分支点处从次要调节途径分叉后通过内体。的分支点被推断为远端的一个共同的泡状出芽事件，这两种途径起源于未成熟的颗粒。通过添加渥曼青霉素，观察到小叶中两种途径均未出现可检测的扰动，并且两种途径均未作为溶酶体组织蛋白原B的重要输出途径。这些发现表明，腮腺腺泡细胞使用低容量，高敏感性的分泌途径进行静息分泌和储备颗粒胞吐作用，一种高容量，低敏感性的途径，用于在进餐期间大量的唾液蛋白输出。类似的策略可用于其他分泌细胞类型。
Resting secretion of salivary proteins by the parotid gland is sustained in situ between periods of eating by parasympathetic stimulation and has been assumed to involve low level granule exocytosis. By using parotid lobules from ad libitum fed rats stimulated with low doses of carbachol as an in vitro analog of resting secretion, we deduce from the composition of discharged proteins that secretion does not involve granule exocytosis. Rather, it derives from two other acinar export routes, the constitutive-like (stimulus-independent) pathway and the minor regulated pathway, which responds to low doses of cholinergic or P-adrenergic agonists (Castle, J, D,, and Castle, A. M. (1996) J, Cell Sci, 109, 2591-2599). The protein composition collected in vitro mimics that collected from cannulated ducts of glands given low level stimulation in situ. Analysis of secretory trafficking along the two pathways of resting secretion has indicated that the constitutive-like pathway may pass through endosomes after diverging from the minor regulated pathway at a brefeldin A sensitive branch point. The branch point is deduced to be distal to a common vesicular budding event by which both pathways originate from immature granules. Detectable perturbation of neither pathway in lobules was observed by wortmannin addition, and neither serves as a significant export route for lysosomal procathepsin B. These findings show that parotid acinar cells use low capacity, high sensitivity secretory pathways for resting secretion and reserve granule exocytosis, a high capacity, low sensitivity pathway, for massive salivary protein export during meals, An analogous strategy may be employed in other secretory cell types.