Recruitment of Tom1L1/Srcasm to Endosomes and the Midbody by Tsg101

Tom1 (target of Myb 1) and its related proteins (Tom1L1/Srcasm and Tom1L2) constitute a protein family, which share an N-terminal VHS (Vps27, Hrs and STAM) domain and a following GAT (GGA and Tom1) domain. Tom1L1 has potential binding sequences for Tsg101, which is one of key regulators of the multivesicular body (MVB) formation. To obtain a clue to the role of Tom1L1 in the MVB formation, we have characterized the Tom1L1-Tsg101 interaction. We have found that not only the PTAP sequence in the GAT domain but also the PSAP sequence in the C-terminal region of Tom1L1 is responsible for its interaction with the UEV domain of Tsg101 and competes with the HIV-1 Gag protein for the Tsg101 interaction. Furthermore, we show that, by means of Tsg101, Tom1L1 associates with the midbody during cytokinesis as well as endosomes. Taken into account the topological equivalency among the events of the MVB formation, viral egress from the cell, and cytokinesis, the data obtained here suggest that Tom1L1 is implicated in these three distinct cellular processes.