PDF(Pubmed)
Abstract：
In the Drosophila larval salivary gland, developmentally programmed fusions between lysosomes and secretory granules (SGs) and their subsequent acidification promote the maturation of SGs that are secreted shortly before puparium formation. Subsequently, ongoing fusions between non-secreted SGs and lysosomes give rise to degradative crinosomes, where the superfluous secretory material is degraded. Lysosomal fusions control both the quality and quantity of SGs, however, its molecular mechanism is incompletely characterized. Here we identify the R-SNARE Ykt6 as a novel regulator of crinosome formation, but not the acidification of maturing SGs. We show that Ykt6 localizes to Lamp1+ carrier vesicles, and forms a SNARE complex with Syntaxin 13 and Snap29 to mediate fusion with SGs. These Lamp1 carriers represent a distinct vesicle population that are functionally different from canonical Arl8+, Cathepsin L+ lysosomes, which also fuse with maturing SGs but are controlled by another SNARE complex composed of Syntaxin 13, Snap29 and Vamp7. Ykt6- and Vamp7-mediated vesicle fusions also determine the fate of SGs, as loss of either of these SNAREs prevents crinosomes from acquiring endosomal PI3P. Our results highlight that fusion events between SGs and different lysosome-related vesicle populations are critical for fine regulation of the maturation and crinophagic degradation of SGs.
摘要：
在果蝇幼虫唾液腺中，溶酶体和分泌颗粒（SGs）之间的发育编程融合及其随后的酸化促进了在post形成前不久分泌的SGs的成熟。随后，非分泌的SGs和溶酶体之间的持续融合会产生降解性海绵体，多余的分泌物质被降解。溶酶体融合体控制SGs的质量和数量，然而,其分子机制特征不完全。在这里，我们确定R-SNAREYkt6是一种新的小囊形成调节剂，但不是成熟SGs的酸化。我们证明Ykt6定位于Lamp1+载体囊泡，并与Syntaxin13和Snap29形成SNARE复合物，以介导与SGs的融合。这些Lamp1载体代表了一个不同的囊泡群体，在功能上与典型的Arl8不同，组织蛋白酶L+溶酶体,它也与成熟的SGs融合，但由另一个由Syntaxin13，Snap29和Vamp7组成的SNARE复合体控制。Ykt6和Vamp7介导的囊泡融合也决定了SGs的命运，因为这些SNARE中的任何一个的丢失都会阻止Crinosome获得内体PI3P。我们的结果强调，SGs与不同溶酶体相关的囊泡种群之间的融合事件对于精细调节SGs的成熟和食性降解至关重要。
