Flotillin-1 mediates neurite branching induced by synaptic adhesion-like molecule 4 in hippocampal neurons.
Proper development of neurons in the hippocampus is essential for learning and memory. Our laboratory previously discovered a family of synaptic adhesion-like molecules (SALMs) which induce neurite outgrowth in this brain region (Wang et al., 2006). Here we establish flotillin-1 (flot-1) as a molecular mediator of neurite branching for SALM4. Knockdown of flot-1 alone in cultured hippocampal neurons using siRNA from 3-7days in vitro (DIV) impaired neurite branching, whereas overexpression of flot-1 during the same time period increased the number of processes and branching. We show that induction of neurite outgrowth by flot-1 depends on amino acids 134-151 as well as lipid raft microdomains, SoHo proteins to regulate the actin cytoskeleton, and the exocyst complex to deliver new membrane proteins to growing neurites. When each of SALMs 1-5 was overexpressed, siRNA knockdown of flot-1 prevented neurite branching by SALM4. Overall, our data reveal a flot-1 signaling pathway for hippocampal neurite branching that is regulated by SALM4.
Swanwick
Catherine Croft
CC
Laboratory of Neurochemistry, National Institute on Deafness & Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Shapiro
Marietta E
ME
Vicini
Stefano
S
Wenthold
Robert J
RJ
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C106354:flotillins; C555156:synaptic adhesion-like molecule 4, rat