Search for novel membrane trafficking pathway involved in autophagy

巨自噬(以下简称自噬)伴随着动态的膜重塑，如自噬小体的形成和自噬小体与溶酶体间的融合。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，即Rab型小GTP酶的失活者，作为自噬小体驻留蛋白，所以在这里我讨论了这些Rab-Gap(OATL1/TBC1D25，TBC1D2B，TBC1D11)在自噬中的功能。它们定位于自噬小体，并与自噬小体驻留蛋白Lc3结合，作为自噬小体的标志。TbC1D2B和TbC1D25需要与Lc3相互作用才能定位在自噬小体上，因为取消相互作用的点突变削弱了它们的定位。虽然我之前发现过表达TBC1D25抑制自噬小体和溶酶体之间的融合，但过表达TBC1D2B和TBC1D11并不抑制任何自噬过程。这些结果到目前为止还没有阐明这些Rab-Gap和自噬之间的关系。然而，我认为Lc3可能作为Rab-Gap的支架，除了在自噬中发挥作用外，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.