PMID- 19238500
OWN - NLM
STAT- MEDLINE
DCOM- 20091109
LR  - 20211020
IS  - 1473-4230 (Electronic)
IS  - 1473-4222 (Linking)
VI  - 8
IP  - 3
DP  - 2009 Sep
TI  - Developmentally regulated Ca2+-dependent activator protein for secretion 2 
      (CAPS2) is involved in BDNF secretion and is associated with autism 
      susceptibility.
PG  - 312-22
LID - 10.1007/s12311-009-0097-5 [doi]
AB  - The postnatal development of the cerebellum is accomplished via a series of 
      cytogenetic and morphogenetic events encoded in the genome. To decipher the 
      underlying genetic basis of these events we have systematized the spatio-temporal 
      gene expression profiles during mouse cerebellar development in the Cerebellar 
      Development Transcriptome Database (CDT-DB). Using the CDT-DB, Ca(2+)-dependent 
      activator protein for secretion 2 (CAPS2 or CADPS2) was identified as a 
      developmentally regulated gene that is predominantly expressed in cerebellar 
      granule cells (GCs) with an expression peak around the first or second postnatal 
      week. CAPS2 protein is concentrated in parallel fiber (PF) terminals and is 
      associated with secretory vesicles containing brain-derived neurotrophic factor 
      (BDNF) and neurotrophin-3 (NT-3). CAPS2 enhances release of BDNF and NT-3, both 
      of which are essential for normal cerebellar development. CAPS2-deficient 
      (CAPS2(-/-)) mice show reduced secretion of BDNF and NT-3; consequently, the 
      cerebella of these mice exhibit developmental deficits, such as delayed 
      development and increased cell death in GCs, fewer branched dendrites on Purkinje 
      cells (PCs), and loss of the intercrural fissure. The PF-PC synapses have 
      aberrant cytoarchitectures and electrophysiological properties. These abnormal 
      cellular and morphological phenotypes are more severe around the cerebellar 
      vermis, in which hypoplasia has been reported in autism patients. Moreover, 
      CAPS2(-/-) mice had fewer cortical and hippocampal parvalbumin-positive 
      interneurons and some autistic-like behavioral phenotypes. In the CAPS2 genes of 
      some autistic patients an aberrant splicing variant and non-synonymous SNPs have 
      been identified. These recent studies implicate CAPS2 in autism susceptibility. 
      Therefore, CAPS2(-/-) mice will be a useful model animal in which to study 
      aspects of the neuropathology and behaviors characteristic of developmental 
      disorders.
FAU - Sadakata, Tetsushi
AU  - Sadakata T
AD  - Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako, 
      Saitama 351-0198, Japan.
FAU - Furuichi, Teiichi
AU  - Furuichi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20090224
PL  - United States
TA  - Cerebellum
JT  - Cerebellum (London, England)
JID - 101089443
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CADPS2 protein, human)
RN  - 0 (CAPS2 protein, mouse)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Animals
MH  - *Autistic Disorder/etiology/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium-Binding Proteins/deficiency/*metabolism
MH  - *Cerebellum/growth & development/metabolism/pathology
MH  - Eliminative Behavior, Animal
MH  - Gene Expression Regulation, Developmental/genetics/*physiology
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/deficiency
MH  - Vesicular Transport Proteins/*metabolism
RF  - 81
EDAT- 2009/02/25 09:00
MHDA- 2009/11/10 06:00
CRDT- 2009/02/25 09:00
PHST- 2008/09/30 00:00 [received]
PHST- 2009/02/05 00:00 [accepted]
PHST- 2009/02/25 09:00 [entrez]
PHST- 2009/02/25 09:00 [pubmed]
PHST- 2009/11/10 06:00 [medline]
AID - 10.1007/s12311-009-0097-5 [doi]
PST - ppublish
SO  - Cerebellum. 2009 Sep;8(3):312-22. doi: 10.1007/s12311-009-0097-5. Epub 2009 Feb 
      24.