First Author | Zhong Z | Year | 2018 |
Journal | EMBO J | Volume | 37 |
Issue | 6 | PubMed ID | 29496740 |
Mgi Jnum | J:261168 | Mgi Id | MGI:6154430 |
Doi | 10.15252/embj.201797822 | Citation | Zhong Z, et al. (2018) Prion-like protein aggregates exploit the RHO GTPase to cofilin-1 signaling pathway to enter cells. EMBO J 37(6) |
abstractText | Protein aggregation is a hallmark of diverse neurodegenerative diseases. Multiple lines of evidence have revealed that protein aggregates can penetrate inside cells and spread like prions. How such aggregates enter cells remains elusive. Through a focused siRNA screen targeting genes involved in membrane trafficking, we discovered that mutant SOD1 aggregates, like viruses, exploit cofilin-1 to remodel cortical actin and enter cells. Upstream of cofilin-1, signalling from the RHO GTPase and the ROCK1 and LIMK1 kinases controls cofilin-1 activity to remodel actin and modulate aggregate entry. In the spinal cord of symptomatic SOD1(G93A) transgenic mice, cofilin-1 phosphorylation is increased and actin dynamics altered. Importantly, the RHO to cofilin-1 signalling pathway also modulates entry of tau and alpha-synuclein aggregates. Our results identify a common host cell signalling pathway that diverse protein aggregates exploit to remodel actin and enter cells. |