PMID- 37316833
OWN - NLM
STAT- MEDLINE
DCOM- 20230616
LR  - 20230702
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 24
IP  - 1
DP  - 2023 Jun 14
TI  - The intermediate filament protein nestin serves as a molecular hub for smooth 
      muscle cytoskeletal signaling.
PG  - 157
LID - 10.1186/s12931-023-02473-8 [doi]
LID - 157
AB  - BACKGROUND: The recruitment of the actin-regulatory proteins cortactin and 
      profilin-1 (Pfn-1) to the membrane is important for the regulation of actin 
      cytoskeletal reorganization and smooth muscle contraction. Polo-like kinase 1 
      (Plk1) and the type III intermediate filament protein vimentin are involved in 
      smooth muscle contraction. Regulation of complex cytoskeletal signaling is not 
      entirely elucidated. The aim of this study was to evaluate the role of nestin (a 
      type VI intermediate filament protein) in cytoskeletal signaling in airway smooth 
      muscle. METHODS: Nestin expression in human airway smooth muscle (HASM) was 
      knocked down by specific shRNA or siRNA. The effects of nestin knockdown (KD) on 
      the recruitment of cortactin and Pfn-1, actin polymerization, myosin light chain 
      (MLC) phosphorylation, and contraction were evaluated by cellular and 
      physiological approaches. Moreover, we assessed the effects of 
      non-phosphorylatable nestin mutant on these biological processes. RESULTS: Nestin 
      KD reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM 
      contraction without affecting MLC phosphorylation. Moreover, contractile 
      stimulation enhanced nestin phosphorylation at Thr-315 and the interaction of 
      nestin with Plk1. Nestin KD also diminished phosphorylation of Plk1 and vimentin. 
      The expression of T315A nestin mutant (alanine substitution at Thr-315) reduced 
      the recruitment of cortactin and Pfn-1, actin polymerization, and HASM 
      contraction without affecting MLC phosphorylation. Furthermore, Plk1 KD 
      diminished nestin phosphorylation at this residue. CONCLUSIONS: Nestin is an 
      essential macromolecule that regulates actin cytoskeletal signaling via Plk1 in 
      smooth muscle. Plk1 and nestin form an activation loop during contractile 
      stimulation.
CI  - (c) 2023. The Author(s).
FAU - Wang, Yinna
AU  - Wang Y
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, 47 New 
      Scotland Avenue, MC-8, Albany, NY, 12208, USA.
FAU - Liao, Guoning
AU  - Liao G
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, 47 New 
      Scotland Avenue, MC-8, Albany, NY, 12208, USA.
FAU - Wu, Yidi
AU  - Wu Y
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, 47 New 
      Scotland Avenue, MC-8, Albany, NY, 12208, USA.
FAU - Wang, Ruping
AU  - Wang R
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, 47 New 
      Scotland Avenue, MC-8, Albany, NY, 12208, USA.
FAU - Tang, Dale D
AU  - Tang DD
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, 47 New 
      Scotland Avenue, MC-8, Albany, NY, 12208, USA. tangd@amc.edu.
LA  - eng
GR  - R01 HL110951/HL/NHLBI NIH HHS/United States
GR  - R01 HL130304/HL/NHLBI NIH HHS/United States
GR  - R01 HL145392/HL/NHLBI NIH HHS/United States
GR  - NHLBI Grants HL-110951/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20230614
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Nestin)
RN  - 0 (Vimentin)
RN  - 0 (Cortactin)
RN  - 0 (Actins)
SB  - IM
MH  - Humans
MH  - Nestin/genetics
MH  - Vimentin
MH  - *Cortactin/genetics
MH  - *Actins
MH  - Cytoskeleton
PMC - PMC10268400
OTO - NOTNLM
OT  - Actin
OT  - Intermediate filaments
OT  - Protein phosphorylation
OT  - Smooth muscle contraction
COIS- The authors declare that they have no competing interests.
EDAT- 2023/06/15 01:08
MHDA- 2023/06/16 06:42
PMCR- 2023/06/14
CRDT- 2023/06/14 23:35
PHST- 2023/05/02 00:00 [received]
PHST- 2023/06/08 00:00 [accepted]
PHST- 2023/06/16 06:42 [medline]
PHST- 2023/06/15 01:08 [pubmed]
PHST- 2023/06/14 23:35 [entrez]
PHST- 2023/06/14 00:00 [pmc-release]
AID - 10.1186/s12931-023-02473-8 [pii]
AID - 2473 [pii]
AID - 10.1186/s12931-023-02473-8 [doi]
PST - epublish
SO  - Respir Res. 2023 Jun 14;24(1):157. doi: 10.1186/s12931-023-02473-8.