AMPK Interacts with DSCAM and Plays an Important Role in Netrin-1 Induced Neurite Outgrowth
Overview
Cell Biology
Affiliations
Down syndrome cell adhesion molecule (DSCAM) acts as a netrin-1 receptor and mediates attractive response of axons to netrin-1 in neural development. However, the signaling mechanisms of netrin-DSCAM remain unclear. Here we report that AMP-activated protein kinase (AMPK) interacts with DSCAM through its γ subunit, but does not interact with DCC (deleted in colorectal cancer), another major receptor for netrin-1. Netrin-treatment of cultured cortical neurons leads to increased phosphorylation of AMPK. Both AMPK mutant with dominant-negative effect and AMPK inhibitor can significantly suppress netrin-1 induced neurite outgrowth. Together, these findings demonstrate that AMPK interacts with DSCAM and plays an important role in netrin-1 induced neurite outgrowth. Our study uncovers a previously unknown component, AMPK, in netrin-DSCAM signaling pathway.
Guo L, Cui J, Wang H, Medina R, Zhang S, Zhang X Mol Ther Oncolytics. 2021; 20:119-131.
PMID: 33575476 PMC: 7851485. DOI: 10.1016/j.omto.2020.11.004.
Di Paolo A, Eastman G, Mesquita-Ribeiro R, Farias J, Macklin A, Kislinger T RNA. 2020; 26(11):1637-1653.
PMID: 32747606 PMC: 7566564. DOI: 10.1261/rna.075424.120.
Protein kinases: master regulators of neuritogenesis and therapeutic targets for axon regeneration.
Bennison S, Blazejewski S, Smith T, Toyo-Oka K Cell Mol Life Sci. 2019; 77(8):1511-1530.
PMID: 31659414 PMC: 7166181. DOI: 10.1007/s00018-019-03336-6.
Wang L, Zhao L, Zhang L, Liu X, Hou X, Gao H Animals (Basel). 2019; 9(9).
PMID: 31461826 PMC: 6770873. DOI: 10.3390/ani9090609.
Revisiting Netrin-1: One Who Guides (Axons).
Boyer N, Gupton S Front Cell Neurosci. 2018; 12:221.
PMID: 30108487 PMC: 6080411. DOI: 10.3389/fncel.2018.00221.