Search for novel membrane trafficking pathway involved in autophagy

巨自噬（Macroautpohagy，以下简称自噬）伴随着动态的膜重构，如自噬体的形成以及自噬体与溶酶体的融合。然而，这种膜重塑的调节在很大程度上是未知的。由于我已经确定了三个Rab-GAP，Rab-type小GTP酶的灭活剂，作为自噬体驻留蛋白，在这里我解决了这些Rab-GAP（OATL 1/TBC 1D 25，TBC 1D 2B，TBC 1D 11）在自噬中的功能。它们定位于自噬体并与LC 3结合，LC 3是一种用作自噬体标记的自噬体驻留蛋白。TBC 1D 2B和TBC 1D 25需要与LC 3相互作用才能在自噬体中定位，因为取消相互作用的点突变会损害它们的定位。虽然我以前发现TBC 1D 25的过表达抑制了自噬体和溶酶体之间的融合，但TBC 1D 2B和TBC 1D 11的过表达并没有抑制自噬的任何过程。然而，我认为LC 3可能作为Rab-GAP的支架，除了在自噬中之外，还在膜运输中发挥作用。

Macroautpohagy (referred to as autophagy hereafter) accompanies dynamic membrane remodeling such as autophagosome formation and fusion between autophagosome and lysosome. However, the regulation of such membrane remodeling is largely unknown. Since I had identified three Rab-GAPs, inactivators of Rab-type small GTPases, as autophagosome resident proteins, here I addressed the function of these Rab-GAPs (OATL1/TBC1D25, TBC1D2B, TBC1D11) in autophagy. They were localized at autophagosomes and bound with LC3, an autophagosome resident protein used as a marker of autophagosome. TBC1D2B and TBC1D25 required the interaction with LC3 for their localization at autophagosomes, since a point mutation that abolished the interaction impaired their localization. Although I previously revealed that overexpression of TBC1D25 inhibits fusion between autophagosomes and lysosomes, overexpression of TBC1D2B nor TBC1D11 did not inhibit any process of autophagy.These results so far did not clarify relationship between these Rab-GAPs and autophagy. However, I suppose that it is possible that LC3 acts as a scaffold for Rab-GAPs and has a role in membrane trafficking in addition to in autophagy.