PMID- 22375002
OWN - NLM
STAT- MEDLINE
DCOM- 20120702
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 18
DP  - 2012 Apr 27
TI  - Protein implicated in nonsyndromic mental retardation regulates protein kinase A 
      (PKA) activity.
PG  - 14644-58
LID - 10.1074/jbc.M111.261875 [doi]
AB  - Mutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which 
      encodes a C2 domain and DM14 domain-containing protein, has been linked to severe 
      autosomal recessive nonsyndromic mental retardation. Using a mouse model that 
      produces a truncated form of CC2D1A that lacks the C2 domain and three of the 
      four DM14 domains, we show that CC2D1A is important for neuronal differentiation 
      and brain development. CC2D1A mutant neurons are hypersensitive to stress and 
      have a reduced capacity to form dendrites and synapses in culture. At the 
      biochemical level, CC2D1A transduces signals to the cyclic adenosine 
      3',5'-monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell 
      differentiation. PKA activity is compromised, and the translocation of its 
      catalytic subunit to the nucleus is also defective in CC2D1A mutant cells. 
      Consistently, phosphorylation of the PKA target cAMP-responsive element-binding 
      protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects 
      in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal 
      primary cells derived from the CC2D1A KO mice. CC2D1A associates with the 
      cAMP-PKA complex following forskolin treatment and accumulates in vesicles or on 
      the plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the 
      PKA complex to the membrane to facilitate signal transduction. Together, our data 
      show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway, 
      which may be the underlying cause for impaired mental function in nonsyndromic 
      mental retardation patients with CC2D1A mutation.
FAU - Al-Tawashi, Azza
AU  - Al-Tawashi A
AD  - Center for Molecular Discovery, Verna and Marrs McLean Department of Biochemistry 
      and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. 
      azza.altawashi@kaust.edu.sa
FAU - Jung, Sung Yun
AU  - Jung SY
FAU - Liu, Dou
AU  - Liu D
FAU - Su, Bing
AU  - Su B
FAU - Qin, Jun
AU  - Qin J
LA  - eng
PT  - Journal Article
DEP - 20120228
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CC2D1A protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Freud-1 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/physiology
MH  - Animals
MH  - Brain/*embryology/metabolism
MH  - Cell Line
MH  - Cell Nucleus/genetics/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Genetic Diseases, Inborn/genetics/metabolism
MH  - Humans
MH  - Intellectual Disability/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neurons/*metabolism
MH  - Protein Structure, Tertiary
MH  - Repressor Proteins/genetics/*metabolism
MH  - Response Elements/physiology
MH  - Signal Transduction/*physiology
PMC - PMC3340277
EDAT- 2012/03/01 06:00
MHDA- 2012/07/03 06:00
PMCR- 2012/02/28
CRDT- 2012/03/01 06:00
PHST- 2012/03/01 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/07/03 06:00 [medline]
PHST- 2012/02/28 00:00 [pmc-release]
AID - S0021-9258(20)47957-8 [pii]
AID - M111.261875 [pii]
AID - 10.1074/jbc.M111.261875 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Apr 27;287(18):14644-58. doi: 10.1074/jbc.M111.261875. Epub 
      2012 Feb 28.