Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
J Cell Biol. 2010 Nov 1;191(3):599-613. doi: 10.1083/jcb.201003021.
Syt VII is a Ca(2+) sensor that regulates lysosome exocytosis and plasma membrane repair. Because it lacks motifs that mediate lysosomal targeting, it is unclear how Syt VII traffics to these organelles. In this paper, we show that mutations or inhibitors that abolish palmitoylation disrupt Syt VII targeting to lysosomes, causing its retention in the Golgi complex. In macrophages, Syt VII is translocated simultaneously with the lysosomal tetraspanin CD63 from tubular lysosomes to nascent phagosomes in a Ca(2+)-dependent process that facilitates particle uptake. Mutations in Syt VII palmitoylation sites block trafficking of Syt VII, but not CD63, to lysosomes and phagosomes, whereas tyrosine replacement in the lysosomal targeting motif of CD63 causes both proteins to accumulate on the plasma membrane. Complexes of CD63 and Syt VII are detected only when Syt VII palmitoylation sites are intact. These findings identify palmitoylation-dependent association with the tetraspanin CD63 as the mechanism by which Syt VII is targeted to lysosomes.
Syt VII 是一种 Ca(2+) 传感器，调节溶酶体胞吐和质膜修复。由于它缺乏介导溶酶体靶向的基序，因此不清楚 Syt VII 如何转运到这些细胞器。在本文中，我们表明，消除棕榈酰化的突变或抑制剂会破坏 Syt VII 对溶酶体的靶向，导致其在高尔基体复合物中滞留。在巨噬细胞中，Syt VII 与溶酶体四跨膜蛋白 CD63 一起从管状溶酶体转位到新形成的吞噬体，这是一个依赖 Ca(2+) 的过程，有助于颗粒摄取。Syt VII 棕榈酰化位点的突变阻止了 Syt VII 但不是 CD63 向溶酶体和吞噬体的转运，而 CD63 溶酶体靶向基序中的酪氨酸取代导致两种蛋白都在质膜上积累。只有当 Syt VII 棕榈酰化位点完整时，才能检测到 CD63 和 Syt VII 的复合物。这些发现确定了棕榈酰化依赖性与四跨膜蛋白 CD63 的关联是 Syt VII 靶向溶酶体的机制。
