PMID- 22662246
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse 
      scaffold proteins in the biological clock.
PG  - e37894
LID - 10.1371/journal.pone.0037894 [doi]
LID - e37894
AB  - The neurexin genes (NRXN1/2/3) encode two families (alpha and beta) of highly 
      polymorphic presynaptic proteins that are involved in excitatory/inhibitory 
      synaptic balance. Recent studies indicate that neuronal activation and memory 
      formation affect NRXN1/2/3alpha expression and alternative splicing at splice sites 3 
      and 4 (SS#3/SS#4). Neurons in the biological clock residing in the 
      suprachiasmatic nuclei of the hypothalamus (SCN) act as self-sustained 
      oscillators, generating rhythms in gene expression and electrical activity, to 
      entrain circadian bodily rhythms to the 24 hours day/night cycles. Cell 
      autonomous oscillations in NRXN1/2/3alpha expression and SS#3/SS#4 exons splicing and 
      their links to rhythms in excitatory/inhibitory synaptic balance in the circadian 
      clock were explored. NRXN1/2/3alpha expression and SS#3/SS#4 splicing, levels of 
      neurexin-2alpha and the synaptic scaffolding proteins PSD-95 and gephyrin 
      (representing excitatory and inhibitory synapses, respectively) were studied in 
      mRNA and protein extracts obtained from SCN of C3H/J mice at different times of 
      the 24 hours day/night cycle. Further studies explored the circadian oscillations 
      in these components and causality relationships in immortalized rat SCN2.2 cells. 
      Diurnal rhythms in mNRXN1alpha and mNRXN2alpha transcription, SS#3/SS#4 exon-inclusion 
      and PSD-95 gephyrin and neurexin-2alpha levels were found in the SCN in vivo. No such 
      rhythms were found with mNRXN3alpha. SCN2.2 cells also exhibited autonomous circadian 
      rhythms in rNRXN1/2 expression SS#3/SS#4 exon inclusion and PSD-95, gephyrin and 
      neurexin-2alpha levels. rNRXN3alpha and rNRXN1/2beta were not expressed. Causal 
      relationships were demonstrated, by use of specific siRNAs, between rNRXN2alpha SS#3 
      exon included transcripts and gephyrin levels in the SCN2.2 cells. These results 
      show for the first time dynamic, cell autonomous, diurnal rhythms in expression 
      and splicing of NRXN1/2 and subsequent effects on the expression of neurexin-2alpha 
      and postsynaptic scaffolding proteins in SCN across the 24-h cycle. NRXNs gene 
      transcripts may have a role in coupling the circadian clock to diurnal rhythms in 
      excitatory/inhibitory synaptic balance.
FAU - Shapiro-Reznik, Mika
AU  - Shapiro-Reznik M
AD  - Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv 
      University, Tel Aviv, Israel.
FAU - Jilg, Anje
AU  - Jilg A
FAU - Lerner, Hadas
AU  - Lerner H
FAU - Earnest, David J
AU  - Earnest DJ
FAU - Zisapel, Nava
AU  - Zisapel N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120525
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Nrxn1 protein, mouse)
RN  - 0 (Period Circadian Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (gephyrin)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Biological Clocks/drug effects/*genetics
MH  - Calcium-Binding Proteins
MH  - Carrier Proteins/metabolism
MH  - Cell Line
MH  - Central Nervous System Depressants/pharmacology
MH  - Circadian Rhythm/drug effects/*genetics
MH  - Disks Large Homolog 4 Protein
MH  - Guanylate Kinases/metabolism
MH  - Male
MH  - Melatonin/pharmacology
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Neural Cell Adhesion Molecules/*genetics/metabolism
MH  - Period Circadian Proteins/genetics
MH  - Protein Transport
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Suprachiasmatic Nucleus/drug effects/metabolism
MH  - Synapses/*metabolism
MH  - *Transcription, Genetic
PMC - PMC3360661
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/05 06:00
MHDA- 2012/12/14 06:00
PMCR- 2012/05/25
CRDT- 2012/06/05 06:00
PHST- 2012/03/02 00:00 [received]
PHST- 2012/04/26 00:00 [accepted]
PHST- 2012/06/05 06:00 [entrez]
PHST- 2012/06/05 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2012/05/25 00:00 [pmc-release]
AID - PONE-D-12-06297 [pii]
AID - 10.1371/journal.pone.0037894 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e37894. doi: 10.1371/journal.pone.0037894. Epub 2012 May 25.