Document Detail

Developmentally regulated alternative splicing in a novel synaptojanin.
MedLine Citation:
PMID:  9442075     Owner:  NLM     Status:  MEDLINE    
Phosphatidylinositol phosphates (PIPs) perform central functions in signal transduction and membrane traffic. Synaptojanin is a PIP 5-phosphatase that is expressed in a brain-specific and a ubiquitous splice variants and is thought to constitute the major PIP 5-phosphatase in mammalian brain (Woscholski, R., Finan, P.M., Radley, E., Totty, N.F., Sterling, A.E., Hsuan, J.J., Waterfield, M. D., and Parker, P. J. (1997) J. Biol. Chem. 272, 9625-9628). We now describe synaptojanin 2, a novel isoform of synaptojanin that, similar to synaptojanin 1, contains an N-terminal SAC1-like sequence and a central 5-phosphatase domain but a distinct, unique C-terminal sequence. Transfection studies demonstrated that synaptojanin 2, like synaptojanin 1, is an active PIP phosphatase. An interesting feature of synaptojanin 1 is the presence of a long open reading frame in the 3' region of the brain mRNA that in non-brain tissues is joined to the coding region by alternative splicing, resulting in a shorter synaptojanin 1 form in brain and a longer form in peripheral tissues (Ramjaun, A. R., and McPherson, P. S. (1996) J. Biol. Chem. 271, 24856-24861). Although it exhibits no homology to synaptojanin 1 in this region, synaptojanin 2 also contains an open reading frame in the 3' region that is subject to alternative splicing. Similar to synaptojanin 1, alternative splicing of synaptojanin 2 is tissue-specific and creates a shorter isoform expressed in brain and a longer form in peripheral tissues. The similar alternative splicing of two homologous proteins in a region of non-homology raises the possibility of evolutionary convergence and supports the significance of the variants. Analysis of mRNAs from three brain regions at different developmental stages revealed that alternative splicing of synaptojanin 2 is a developmentally late event, occurring only after the first postnatal week after the generation of neurons and initial synaptogenesis.
M Khvotchev; T C Südhof
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  273     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-03-03     Completed Date:  1998-03-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2306-11     Citation Subset:  IM    
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
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MeSH Terms
Alternative Splicing*
Amino Acid Sequence
Base Sequence
Brain / metabolism
Cloning, Molecular
Enzyme Inhibitors / chemistry
Gene Library
Molecular Sequence Data
Nerve Tissue Proteins / chemistry,  genetics*
Phosphatidylinositol Phosphates / physiology
Phospholipase D / antagonists & inhibitors
Phosphoric Monoester Hydrolases / chemistry,  genetics*
Signal Transduction
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nerve Tissue Proteins; 0/Phosphatidylinositol Phosphates; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.-/synaptojanin; EC D

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