Cargo selectivity of the mammalian COPII coat complex

描述(申请人提供)：真核细胞的一个标志是细胞功能在膜封闭的细胞器内的区隔。小(直径50-100 nm)的囊泡在运输选定的货物蛋白质和脂肪分子的细胞器之间运输。选择性转运确保细胞器组成的维持，是关键细胞过程的基本机制，如内吞作用、分泌功能以及激素和神经递质的胞吐作用。COPII包衣复合体通过将新合成的蛋白质结合到内质网(ER)中萌发的小泡中，并与早期高尔基体之间的融合，介导了分泌运输的第一步。目前的建议试图使用生化和X射线结晶学方法相结合的方法来研究哺乳动物COPII复合体选择货物的分子决定因素。具体地说，该提案旨在研究具有重要生物学意义的哺乳动物货物分子，包括：分泌生长因子、圈套、细胞表面受体和膜通道。最终目的是提供所有哺乳动物ER输出基序的分子水平描述及其与COPII外壳复合体的相互作用。

DESCRIPTION (provided by applicant): A hallmark of eukaryotic cells is the compartmentalization of cellular functions within membrane-enclosed organelles. Small (50-100 nm diameter) vesicles traffic between organelles transporting select cargo protein and lipid molecules. Selective transport ensures the maintenance of the organelle composition and is the underlying mechanism of key cellular processes such as endocytosis, secretory function, and exocytosis of hormones and neurotransmitters. The COPII coat complex mediates the first step in secretory traffic by incorporating newly synthesized proteins into vesicles that bud from the endoplasmic reticulum (ER) and fuse with early Golgi compartments. The current proposal seeks to study the molecular determinants of cargo selection by the mammalian COPII complex using a combination of biochemical and X-ray crystallographic methods. Specifically, the proposal aims to study biologically important mammalian cargo molecules including: secreted growth factors, SNAREs, cell surface receptors, and membrane channels. The ultimate aim is to provide a molecular level description of all mammalian ER export motifs and their interaction with the COPII coat complex.