Journal
JOURNAL OF CELL BIOLOGY
Volume 221, Issue 10, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202203048
Keywords
-
Categories
Funding
- National Research Foundation of Korea [2019R1A2C2089437, 2021M3E5D9021887, 2021R1A4A1021594, 2022R1A2B5B02002598]
- National Research Foundation of Korea [2021M3E5D9021887, 2019R1A2C2089437, 2022R1A2B5B02002598, 2021R1A4A1021594] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Modulation of presynaptic actin dynamics is crucial for synaptic growth and functional plasticity. The Rho-type GEF Vav inhibits synaptic growth through macropinocytosis and plays a role in synaptic plasticity. The Vav-Rac1-SCAR signaling pathway independently regulates structural and functional presynaptic plasticity by driving macropinocytosis and mobilization of reserve pool vesicles.
Modulation of presynaptic actin dynamics is fundamental to synaptic growth and functional plasticity; yet the underlying molecular and cellular mechanisms remain largely unknown. At Drosophila NMJs, the presynaptic Rac1-SCAR pathway mediates BMP-induced receptor macropinocytosis to inhibit BMP growth signaling. Here, we show that the Rho-type GEF Vav acts upstream of Rac1 to inhibit synaptic growth through macropinocytosis. We also present evidence that Vav-Rac1-SCAR signaling has additional roles in tetanus-induced synaptic plasticity. Presynaptic inactivation of Vav signaling pathway components, but not regulators of macropinocytosis, impairs post-tetanic potentiation (PTP) and enhances synaptic depression depending on external Ca2+ concentration. Interfering with the Vav-Rac1-SCAR pathway also impairs mobilization of reserve pool (RP) vesicles required for tetanus-induced synaptic plasticity. Finally, treatment with an F-actin-stabilizing drug completely restores RP mobilization and plasticity defects in Vav mutants. We propose that actin-regulatory Vav-Rac1-SCAR signaling independently regulates structural and functional presynaptic plasticity by driving macropinocytosis and RP mobilization, respectively.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available