RAB26 coordinates lysosome traffic and mitochondrial localization
RAB26 coordinates lysosome traffic and mitochondrial localization
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DOI：
10.1242/jcs.138776
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
Mills, Jason C.
中科院分区：
文献类型：
--
作者：
Jin, Ramon U.;Mills, Jason C.
随着成熟，专业的分泌细胞，如胰腺腺泡细胞和胃主细胞，诱导转录因子MIST1(也称为BHLHA15)在涉及顶端细胞质扩张和溶酶体和线粒体重新分布的过程中大幅增加大分泌颗粒的产生。像MIST1这样的伸缩因子如何仅仅通过调节其转录靶标的表达水平来重新排列细胞结构尚不清楚。RAB26是一个MIST1靶点，其在MIST1介导的分泌细胞成熟中的作用也是未知的。在这里，我们证实RAB26的表达，不像大多数RAB普遍表达，是组织特异性的，主要限于表达MIST1的分泌组织。令人惊讶的是，功能研究表明RAB26主要与LAMP1/组织蛋白酶D溶酶体相关，而不是直接与分泌颗粒相关。此外，增加RAB26的表达--通过诱导酶原分泌细胞的分化或直接转染法--会导致溶酶体在中央的核周区域聚集。溶酶体聚集反过来又导致线粒体重新分布到不同的亚细胞邻域。这些数据阐明了RAB26的一项新功能，并暗示了细胞如何在分化过程中增加关键效应物的转录以重组亚细胞室的机制。
As they mature, professional secretory cells like pancreatic acinar and gastric chief cells induce the transcription factor MIST1 (also known as BHLHA15) to substantially scale up production of large secretory granules in a process that involves expansion of apical cytoplasm and redistribution of lysosomes and mitochondria. How a scaling factor like MIST1 rearranges cellular architecture simply by regulating expression levels of its transcriptional targets is unknown. RAB26 is a MIST1 target whose role in MIST1-mediated secretory cell maturation is also unknown. Here, we confirm that RAB26 expression, unlike most Rabs which are ubiquitously expressed, is tissue specific and largely confined to MIST1-expressing secretory tissues. Surprisingly, functional studies showed that RAB26 predominantly associated with LAMP1/cathepsin D lysosomes and not directly with secretory granules. Moreover, increasing RAB26 expression - by inducing differentiation of zymogen-secreting cells or by direct transfection - caused lysosomes to coalesce in a central, perinuclear region. Lysosome clustering in turn caused redistribution of mitochondria into distinct subcellular neighborhoods. The data elucidate a novel function for RAB26 and suggest a mechanism for how cells could increase transcription of key effectors to reorganize subcellular compartments during differentiation.