Figure 6.

Proposed regulatory mechanisms for cargo selection for BicD2/dynein-dependent transport events. (A, B) BicD2 switches between recognizing vesicles and the nucleus for transport in a cell cycle-specific manner. (A) During the G1 and S phases, BicD2 mainly recognizes Rab6-positive secretory and Golgi-derived vesicles as cargo for transport.¹¹ (B) The cell nucleus is recognized as cargo for dynein by BicD2 specifically in G2 phase.¹¹ (C) In the G1 and S phases, BicD2 predominantly recruits dynein to Rab6-positive vesicles. Since the affinity of Nup358 toward BicD2 is high, a negative regulatory mechanism is likely required to avert BicD2 recruitment to the nucleus outside of G2 phase. A candidate is RanGTP; however, an additional negative regulator likely remains to be identified. (D) Our results suggest that the affinity of Nup358 is strong enough to efficiently compete with Rab6a^GTP for BicD2. Therefore, in the absence of negative regulation, Nup358 is expected to recruit ~1000 BicD2 molecules to the nucleus.