PMID- 37169020
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230514
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 11
DP  - 2023
TI  - Interaction of LARP4 to filamin A mechanosensing domain regulates cell 
      migrations.
PG  - 1152109
LID - 10.3389/fcell.2023.1152109 [doi]
LID - 1152109
AB  - Filamin A (FLNA) is an actin cross-linking protein that mediates 
      mechanotransduction. Force-dependent conformational changes of FLNA molecule 
      expose cryptic binding site of FLNA, allowing interaction with partners such as 
      integrin, smoothelin, and fimbacin. Here, we identified La-related protein 4 
      (LARP4) as a new FLNA mechanobinding partner. LARP4 specifically interacts with 
      the cleft formed by C and D strands of immunoglobulin-like repeat 21 (R21) which 
      is blocked by A strand of R20 without force. We validated the interaction between 
      LARP4 and FLNA R21 both in vivo and in vitro. We also determined the critical 
      amino acid that is responsible for the interaction and generated the 
      non-FLNA-binding mutant LARP4 (F277A in human: F273A in mouse Larp4) that 
      disrupts the interaction. Fluorescence recovery after photobleaching (FRAP) of 
      GFP-labeled LARP4 in living cells demonstrated that mutant LARP4 diffuses faster 
      than WT LARP4. Proximity ligation assay (PLA) also confirmed their interaction 
      and disruption of actin polymerization diminishes the interaction. Data mining of 
      RNAseq analysis of LARP4 knockdown (KD) HEK293T cells suggested that LARP4 is 
      involved in morphogenesis and cell motility. Consistent with this prediction, we 
      found that KD of LARP4 increases cell migration speed and expression of the F277A 
      mutant LARP4 in LARP4-KD cells also leads to a higher cell migration speed 
      compared to WT LARP4. These results demonstrated that the LARP4 interaction with 
      FLNA regulates cell migration.
CI  - Copyright (c) 2023 Mao and Nakamura.
FAU - Mao, Zhenfeng
AU  - Mao Z
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      China.
FAU - Nakamura, Fumihiko
AU  - Nakamura F
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230424
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC10164935
OTO - NOTNLM
OT  - FRAP
OT  - LARP4
OT  - cell migration
OT  - filamin A
OT  - mechanotransduction
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/12 01:07
MHDA- 2023/05/12 01:08
PMCR- 2023/01/01
CRDT- 2023/05/11 19:31
PHST- 2023/01/27 00:00 [received]
PHST- 2023/04/14 00:00 [accepted]
PHST- 2023/05/12 01:08 [medline]
PHST- 2023/05/12 01:07 [pubmed]
PHST- 2023/05/11 19:31 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 1152109 [pii]
AID - 10.3389/fcell.2023.1152109 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2023 Apr 24;11:1152109. doi: 10.3389/fcell.2023.1152109. 
      eCollection 2023.