PMID- 36674445
OWN - NLM
STAT- MEDLINE
DCOM- 20230126
LR  - 20240304
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 2
DP  - 2023 Jan 4
TI  - The KDET Motif in the Intracellular Domain of the Cell Adhesion Molecule L1 
      Interacts with Several Nuclear, Cytoplasmic, and Mitochondrial Proteins Essential 
      for Neuronal Functions.
LID - 10.3390/ijms24020932 [doi]
LID - 932
AB  - Abnormal functions of the cell adhesion molecule L1 are linked to several neural 
      diseases. Proteolytic L1 fragments were reported to interact with nuclear and 
      mitochondrial proteins to regulate events in the developing and the adult nervous 
      system. Recently, we identified a 55 kDa L1 fragment (L1-55) that interacts with 
      methyl CpG binding protein 2 (MeCP2) and heterochromatin protein 1 (HP1) via the 
      KDET motif. We now show that L1-55 also interacts with histone H1.4 (HistH1e) via 
      this motif. Moreover, we show that this motif binds to NADH dehydrogenase 
      ubiquinone flavoprotein 2 (NDUFV2), splicing factor proline/glutamine-rich 
      (SFPQ), the non-POU domain containing octamer-binding protein (NonO), paraspeckle 
      component 1 (PSPC1), WD-repeat protein 5 (WDR5), heat shock cognate protein 71 
      kDa (Hsc70), and synaptotagmin 1 (SYT1). Furthermore, applications of HistH1e, 
      NDUFV2, SFPQ, NonO, PSPC1, WDR5, Hsc70, or SYT1 siRNAs or a cell-penetrating 
      KDET-carrying peptide decrease L1-dependent neurite outgrowth and the survival of 
      cultured neurons. These findings indicate that L1's KDET motif binds to an 
      unexpectedly large number of molecules that are essential for nervous 
      system-related functions, such as neurite outgrowth and neuronal survival. In 
      summary, L1 interacts with cytoplasmic, nuclear and mitochondrial proteins to 
      regulate development and, in adults, the formation, maintenance, and flexibility 
      of neural functions.
FAU - Kleene, Ralf
AU  - Kleene R
AD  - Zentrum fur Molekulare Neurobiologie, Universitatsklinikum Hamburg-Eppendorf, 
      Martinistr. 52, 20246 Hamburg, Germany.
FAU - Loers, Gabriele
AU  - Loers G
AD  - Zentrum fur Molekulare Neurobiologie, Universitatsklinikum Hamburg-Eppendorf, 
      Martinistr. 52, 20246 Hamburg, Germany.
FAU - Schachner, Melitta
AU  - Schachner M
AD  - Keck Center for Collaborative Neuroscience, Department of Cell Biology and 
      Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA.
LA  - eng
PT  - Journal Article
DEP - 20230104
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Neural Cell Adhesion Molecule L1)
RN  - 0 (L1CAM protein, human)
SB  - IM
MH  - Cytoplasm/metabolism
MH  - Cytosol/metabolism
MH  - *Mitochondrial Proteins/chemistry/metabolism
MH  - *Neural Cell Adhesion Molecule L1/chemistry/metabolism
MH  - Neurites/metabolism
MH  - Neurons/metabolism
MH  - Humans
MH  - Mice
MH  - Animals
PMC - PMC9866381
OTO - NOTNLM
OT  - KDET motif
OT  - cell adhesion molecule L1
OT  - neurite outgrowth
OT  - neuronal survival
OT  - proteolytic processing
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/01/04
CRDT- 2023/01/21 01:24
PHST- 2022/11/29 00:00 [received]
PHST- 2022/12/30 00:00 [revised]
PHST- 2022/12/31 00:00 [accepted]
PHST- 2023/01/21 01:24 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/04 00:00 [pmc-release]
AID - ijms24020932 [pii]
AID - ijms-24-00932 [pii]
AID - 10.3390/ijms24020932 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 4;24(2):932. doi: 10.3390/ijms24020932.