Redundancies among vesicle transport level-3 sibling SCPs.

To analyze the relationships between Level-3 SCPs, we used our analytical solution to predict steady state dynamics that enable neurite outgrowth for specified velocities. (A), (B) & (C) Level-3 SCPs show complementary relationships between their activities to generate higher level SCP function without violation of the model constraints. (A) Different activities of the SCPs Coat Recruitment and Formation at TGN and Vesicle Invagination and Scission at TGN were modeled by changing the amount of Recruitment Factor 1 and the budding rate at the TGN. SCP activities were inversely related and increased with increasing velocity. Line colors indicate selected velocities as shown in (G). (B) A similar SCP redundancy was observed for the SCPs Kinesin Recruitment to Vesicle (simulated by # number of kinesin receptors) and Kinesin Mediated Vesicle Transport along the MT (simulated by fraction of bound kinesin). (C) Inverse relationship between SCP activities was also observed for the SCPs Vesicle Tethering (simulated via the tethering rate at the GC) and Vesicle Fusion (simulated by amount # of v-SNARE V). (D) Velocities were color coded in each figure as indicated. (E) & (F) The more a Level-2 SCP activity is generated by a Level-3 SCP that contains a vesicle membrane protein, the higher the SCP activity of membrane protein production to compensate for the loss of membrane protein in the growing NSC reservoir. (E) In dependence of the selected fraction of MT-bound kinesin, vesicles need a different amount of kinesin receptors to ensure NOG without violation of the model constraints. A higher kinesin receptor concentration per vesicle directly translates into the need for a higher kinesin production rate. Lines refer to pre-defined fractions of MT-bound kinesin: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 (from top to bottom). (F) Different tethering rates demand different v-SNARE V concentrations per vesicle and consequently different V production rates to ensure NOG without violation of the model constraints (t-SNARE Y is kept constant). Lines refer to different tethering rates: 2.5 x10-6, 3 x10-6, 3.5 x10-6, 4 x10-6, 4.5 x10-6, 5 x10-6 (from top to bottom).