title: Activity-dependent regulation of dendritic complexity by semaphorin 3A through Farp1.
abstract: Dendritic arbors are complex neuronal structures that receive and process synaptic inputs. One mechanism regulating dendrite differentiation is Semaphorin/Plexin signaling, specifically through binding of soluble Sema3A to Neuropilin/PlexinA coreceptors. Here we show that the protein Farp1 [FERM, RhoGEF (ARHGEF), and pleckstrin domain protein 1], a Rac1 activator previously identified as a synaptogenic signaling protein, contributes to establishing dendrite tip number and total dendritic branch length in maturing rat neurons and is sufficient to promote dendrite complexity. Aiming to define its upstream partners, our results support that Farp1 interacts with the Neuropilin-1/PlexinA1 complex and colocalizes with PlexinA1 along dendritic shafts. Functionally, Farp1 is required by Sema3A to promote dendritic arborization of hippocampal neurons, and Sema3A regulates dendritic F-actin distribution via Farp1. Unexpectedly, Sema3A also requires neuronal activity to promote dendritic complexity, presumably because silencing neurons leads to a proteasome-dependent reduction of PlexinA1 in dendrites. These results provide new insights into how activity and soluble cues cooperate to refine dendritic morphology through intracellular signaling pathways.
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, and Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06520.
authors.forename: Lucas
authors.identifier: http://orcid.org/0000-0001-6484-9984
authors.initials: L
authors.lastname: Cheadle
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, and thomas.biederer@tufts.edu.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0003-0912-1514
authors.initials: T
authors.lastname: Biederer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection
chemical_list: D018756:GABA Antagonists; D046912:Multiprotein Complexes; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D064067:Rho Guanine Nucleotide Exchange Factors; D040121:Semaphorin-3A; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C577227:FARP1 protein, human