Bicaudal D acts as a sensor to enable dynein-kinesin co-dependence

Area of Science:

• Cell Biology
• Molecular Motors
• Intracellular Transport

Background:

• Cellular cargoes move bidirectionally along microtubules via dynein (minus-end) and kinesin (plus-end) motors.
• The "paradox of co-dependence," where loss of one motor halts bidirectional movement, lacks a clear molecular explanation.

Purpose of the Study:

• Investigate the molecular mechanism behind the co-dependence of opposing motors in cellular transport.
• Elucidate how dynein and kinesin motors interact and influence each other's function.

Main Methods:

• Utilized a model system with dynein/dynactin and kinesin motors activated by the adaptor BicD.
• Examined the effect of simultaneously binding opposing motors on cargo transport dynamics, including run length and complex assembly.

Main Results:

• Simultaneous binding of opposing motors to BicD significantly increased run lengths due to enhanced recruitment of active motors.
• A BicD point mutant (BicD^F684I) abolished this run length increase, indicating a sensing mechanism involving BicD's coiled-coil structure.
• Opposing motors accelerated the assembly and increased the stability of motile transport complexes.

Conclusions:

• The co-dependence of opposing motors is not paradoxical but a cellular strategy for efficient transport.
• Motor-motor interactions, potentially regulated by BicD structure, enhance the recruitment and stability of transport complexes.
• This mechanism optimizes intracellular cargo movement by ensuring robust and efficient transport dynamics.