Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 9, Pages 1802-1814Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.184580
Keywords
Hippocampus; Semaphorin 3A; NGF; TrkA; PlexA4; Axonal transport
Categories
Funding
- Targeted Proteins Research Program [0761890004]
- Global COE Program
- Innovative Integration between Medicine and Engineering Based on Information Communication Technology [1542140002]
- Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Ministry of Education, Science, Sports and Culture [42890001]
- Japan Society for the Promotion of Science (JSPS) [21700411, 24500444]
- JSPS postdoctoral fellowship
- [17082006]
- Grants-in-Aid for Scientific Research [21700411] Funding Source: KAKEN
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Semaphorin 3A (Sema3A), a secretory semaphorin, exerts various biological actions through a complex between neuropilin-1 and plexin-As (PlexAs). Sema3A induces retrograde signaling, which is involved in regulating dendritic localization of GluA2 (also known as GRIA2), an AMPA receptor subunit. Here, we investigated a possible interaction between retrograde signaling pathways for Sema3A and nerve growth factor (NGF). Sema3A induces colocalization of PlexA4 (also known as PLXNA4) signals with those of tropomyosin-related kinase A (TrkA, also known as NTRK1) in growth cones, and these colocalized signals were then observed along the axons. The time-lapse imaging of PlexA4 and several TrkA mutants showed that the kinase and dynein-binding activity of TrkA were required for Sema3A-induced retrograde transport of the PlexA4-TrkA complex along the axons. The inhibition of the phosphoinositide 3-kinase (PI3K)-Akt signal, a downstream signaling pathway of TrkA, in the distal axon suppressed Sema3A-induced dendritic localization of GluA2. The knockdown of TrkA suppressed Sema3A-induced dendritic localization of GluA2 and that suppressed Sema3A-regulated dendritic branching both in vitro and in vivo. These findings suggest that by interacting with PlexA4, TrkA plays a crucial role in redirecting local Sema3A signaling to retrograde axonal transport, thereby regulating dendritic GluA2 localization and patterning.
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