Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines

Natsumi Ageta-Ishihara; Yugo Fukazawa; Fumiko Arima-Yoshida; Hiroyuki Okuno; Yuichiro Ishii; Keizo Takao; Kohtarou Konno; Kazuto Fujishima; Hiroshi Ageta; Hiroyuki Hioki; Kunihiro Tsuchida; Yoshikatsu Sato; Mineko Kengaku; Masahiko Watanabe; Ayako M. Watabe; Toshiya Manabe; Tsuyoshi Miyakawa; Kaoru Inokuchi; Haruhiko Bito; Makoto Kinoshita

doi:10.1016/j.celrep.2025.115352

Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines

Natsumi Ageta-Ishihara^*, Yugo Fukazawa, Fumiko Arima-Yoshida, Hiroyuki Okuno, Yuichiro Ishii, Keizo Takao, Kohtarou Konno, Kazuto Fujishima, Hiroshi Ageta, Hiroyuki Hioki, Kunihiro Tsuchida, Yoshikatsu Sato, Mineko Kengaku, Masahiko Watanabe, Ayako M. Watabe, Toshiya Manabe, Tsuyoshi Miyakawa, Kaoru Inokuchi, Haruhiko Bito, Makoto Kinoshita^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca²⁺ responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3^−/−) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.

Original language	English
Article number	115352
Journal	Cell Reports
Volume	44
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2025.115352
State	Published - 2025/03/25

Keywords

CP: Cell biology
CP: Neuroscience
L-LTP
cytoskeleton
dendritic spine
memory consolidation
sER
septin
smooth endoplasmic reticulum

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2025.115352

Cite this

Ageta-Ishihara, N., Fukazawa, Y., Arima-Yoshida, F., Okuno, H., Ishii, Y., Takao, K., Konno, K., Fujishima, K., Ageta, H., Hioki, H., Tsuchida, K., Sato, Y., Kengaku, M., Watanabe, M., Watabe, A. M., Manabe, T., Miyakawa, T., Inokuchi, K., Bito, H., & Kinoshita, M. (2025). Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines. Cell Reports, 44(3), Article 115352. https://doi.org/10.1016/j.celrep.2025.115352

@article{01688e0af5564909a0c485688c14f40a,

title = "Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines",

abstract = "Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca2+ responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3−/−) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.",

keywords = "CP: Cell biology, CP: Neuroscience, L-LTP, cytoskeleton, dendritic spine, memory consolidation, sER, septin, smooth endoplasmic reticulum",

author = "Natsumi Ageta-Ishihara and Yugo Fukazawa and Fumiko Arima-Yoshida and Hiroyuki Okuno and Yuichiro Ishii and Keizo Takao and Kohtarou Konno and Kazuto Fujishima and Hiroshi Ageta and Hiroyuki Hioki and Kunihiro Tsuchida and Yoshikatsu Sato and Mineko Kengaku and Masahiko Watanabe and Watabe, {Ayako M.} and Toshiya Manabe and Tsuyoshi Miyakawa and Kaoru Inokuchi and Haruhiko Bito and Makoto Kinoshita",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = mar,

day = "25",

doi = "10.1016/j.celrep.2025.115352",

language = "英語",

volume = "44",

journal = "Cell Reports",

issn = "2639-1856",

publisher = "Elsevier BV",

number = "3",

}

Ageta-Ishihara, N, Fukazawa, Y, Arima-Yoshida, F, Okuno, H, Ishii, Y, Takao, K, Konno, K, Fujishima, K, Ageta, H, Hioki, H, Tsuchida, K, Sato, Y, Kengaku, M, Watanabe, M, Watabe, AM, Manabe, T, Miyakawa, T, Inokuchi, K, Bito, H & Kinoshita, M 2025, 'Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines', Cell Reports, vol. 44, no. 3, 115352. https://doi.org/10.1016/j.celrep.2025.115352

TY - JOUR

T1 - Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines

AU - Ageta-Ishihara, Natsumi

AU - Fukazawa, Yugo

AU - Arima-Yoshida, Fumiko

AU - Okuno, Hiroyuki

AU - Ishii, Yuichiro

AU - Takao, Keizo

AU - Konno, Kohtarou

AU - Fujishima, Kazuto

AU - Ageta, Hiroshi

AU - Hioki, Hiroyuki

AU - Tsuchida, Kunihiro

AU - Sato, Yoshikatsu

AU - Kengaku, Mineko

AU - Watanabe, Masahiko

AU - Watabe, Ayako M.

AU - Manabe, Toshiya

AU - Miyakawa, Tsuyoshi

AU - Inokuchi, Kaoru

AU - Bito, Haruhiko

AU - Kinoshita, Makoto

PY - 2025/3/25

Y1 - 2025/3/25

N2 - Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca2+ responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3−/−) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.

AB - Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca2+ responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3−/−) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.

KW - CP: Cell biology

KW - CP: Neuroscience

KW - L-LTP

KW - cytoskeleton

KW - dendritic spine

KW - memory consolidation

KW - sER

KW - septin

KW - smooth endoplasmic reticulum

UR - http://www.scopus.com/inward/record.url?scp=105000575111&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2025.115352

DO - 10.1016/j.celrep.2025.115352

M3 - 学術論文

C2 - 40023151

AN - SCOPUS:105000575111

SN - 2639-1856

VL - 44

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 115352

ER -