PMID- 36475946
OWN - NLM
STAT- MEDLINE
DCOM- 20221215
LR  - 20230608
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 119
IP  - 50
DP  - 2022 Dec 13
TI  - Septins mediate a microtubule-actin crosstalk that enables actin growth on 
      microtubules.
PG  - e2202803119
LID - 10.1073/pnas.2202803119 [doi]
LID - e2202803119
AB  - Cellular morphogenesis and processes such as cell division and migration require 
      the coordination of the microtubule and actin cytoskeletons. Microtubule-actin 
      crosstalk is poorly understood and largely regarded as the capture and regulation 
      of microtubules by actin. Septins are filamentous guanosine-5'-triphosphate (GTP) 
      binding proteins, which comprise the fourth component of the cytoskeleton along 
      microtubules, actin, and intermediate filaments. Here, we report that septins 
      mediate microtubule-actin crosstalk by coupling actin polymerization to 
      microtubule lattices. Superresolution and platinum replica electron microscopy 
      (PREM) show that septins localize to overlapping microtubules and actin filaments 
      in the growth cones of neurons and non-neuronal cells. We demonstrate that 
      recombinant septin complexes directly crosslink microtubules and actin filaments 
      into hybrid bundles. In vitro reconstitution assays reveal that microtubule-bound 
      septins capture and align stable actin filaments with microtubules. Strikingly, 
      septins enable the capture and polymerization of growing actin filaments on 
      microtubule lattices. In neuronal growth cones, septins are required for the 
      maintenance of the peripheral actin network that fans out from microtubules. 
      These findings show that septins directly mediate microtubule interactions with 
      actin filaments, and reveal a mechanism of microtubule-templated actin growth 
      with broader significance for the self-organization of the cytoskeleton and 
      cellular morphogenesis.
FAU - Nakos, Konstantinos
AU  - Nakos K
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Alam, Md Noor A
AU  - Alam MNA
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Radler, Megan R
AU  - Radler MR
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Kesisova, Ilona A
AU  - Kesisova IA
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Yang, Changsong
AU  - Yang C
AD  - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
FAU - Okletey, Joshua
AU  - Okletey J
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Tomasso, Meagan R
AU  - Tomasso MR
AD  - Department of Biochemistry and Molecular Biology, Drexel University College of 
      Medicine, Philadelphia, PA 19102.
FAU - Padrick, Shae B
AU  - Padrick SB
AUID- ORCID: 0000-0002-6916-6194
AD  - Department of Biochemistry and Molecular Biology, Drexel University College of 
      Medicine, Philadelphia, PA 19102.
FAU - Svitkina, Tatyana M
AU  - Svitkina TM
AD  - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
FAU - Spiliotis, Elias T
AU  - Spiliotis ET
AUID- ORCID: 0000-0003-1082-9763
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
LA  - eng
GR  - R01 GM097664/GM/NIGMS NIH HHS/United States
GR  - R35 GM136337/GM/NIGMS NIH HHS/United States
GR  - R35 GM140832/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221207
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 3.6.1.- (Septins)
RN  - 0 (Actins)
SB  - IM
MH  - *Septins
MH  - *Actins
MH  - Microtubules
PMC - PMC9897426
OTO - NOTNLM
OT  - actin
OT  - actin-microtubule crosstalk
OT  - growth cones
OT  - microtubules
OT  - septins
COIS- The authors declare no competing interest.
EDAT- 2022/12/09 06:00
MHDA- 2022/12/15 06:00
PMCR- 2023/06/07
CRDT- 2022/12/08 09:57
PHST- 2022/12/08 09:57 [entrez]
PHST- 2022/12/09 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2023/06/07 00:00 [pmc-release]
AID - 202202803 [pii]
AID - 10.1073/pnas.2202803119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2202803119. doi: 
      10.1073/pnas.2202803119. Epub 2022 Dec 7.