Mechanism of Arp2/3 complex branch disassembly by human Coro7

Area of Science:

• Cell Biology
• Biochemistry
• Structural Biology

Background:

• The Arp2/3 complex is crucial for forming branched actin networks, essential for cell motility and intracellular transport.
• Coronins are known inhibitors of the Arp2/3 complex, influencing actin branch density.
• Coro7, a less-studied coronin member, possesses distinct structural domains (β1β2 and CA) requiring further investigation.

Purpose of the Study:

• To elucidate the molecular mechanism of Coro7's interaction with the Arp2/3 complex.
• To determine Coro7's role in actin dynamics and its functional implications in cellular processes.
• To investigate the specific contributions of Coro7's domains to its function.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine structural details.
• Biochemical assays to assess binding affinities and polymerization inhibition/induction.
• Cellular experiments involving protein depletion and rescue assays to evaluate functional impact.

Main Results:

• The Coro7 Central-Acidic (CA) domain binds to the Arp3 subunit of the Arp2/3 complex, inhibiting polymerization.
• Full-length Coro7, unlike its isolated domains, acts as an Arp2/3 complex branch disassembly factor.
• Coro7 depletion disrupts endoplasmic reticulum-Golgi transport; this defect is rescued by full-length Coro7 in cellular models.

Conclusions:

• Coro7 functions as a novel Arp2/3 complex branch disassembly factor.
• Coro7 plays a significant role in actin-dependent ER-Golgi trafficking.
• The distinct functions of full-length Coro7 versus its domains highlight the importance of its complete structure for cellular roles.