Characterisation of inosine monophosphate dehydrogenase expression during retinal development: Differences between variants and isoforms
Autor: | Jennifer H. Gunter, Elaine C. Thomas, Jonathan P. Whitehead, Nigel L. Barnett, Leah E. Worton, Edith M. Gardiner, Sarah J. Kruger, Nadia Lengefeld, Alun Jones |
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Rok vydání: | 2008 |
Předmět: |
Gene isoform
Cellular differentiation Intracellular Space CBS domain CHO Cells Biology Biochemistry Gene Expression Regulation Enzymologic Mass Spectrometry Retina Cricetulus IMP Dehydrogenase Antibody Specificity IMP dehydrogenase Cricetinae Retinitis pigmentosa medicine Animals Humans Cloning Molecular Gene Expression Regulation Developmental Reproducibility of Results Cell Biology medicine.disease Rats Cell biology Enzyme Activation Isoenzymes medicine.anatomical_structure Hypoxanthine-guanine phosphoribosyltransferase Mutation sense organs Intracellular |
Zdroj: | The International Journal of Biochemistry & Cell Biology. 40:1716-1728 |
ISSN: | 1357-2725 |
DOI: | 10.1016/j.biocel.2007.12.018 |
Popis: | In mammals there are two ubiquitous, catalytically indistinguishable isoforms of inosine monophosphate dehydrogenase and mutations in the type I isoform, but not type II, cause retina-specific disorders. We have characterised the spatio-temporal expression of these proteins during development of the rat retina and performed functional investigations of the recently described retinal type I variants. Inosine monophosphate dehydrogenase was present in all immature cells throughout the retina during embryonic and neonatal development. Following eye opening and cell differentiation its distribution was restricted to the photoreceptors and bipolar cells, becoming prominent in Müller cells with aging. Type II was present in early, developing retinae whilst type I was undetectable. An isoform switch occurred around P10, after which the type I variants, type Ialpha and type Igamma, were the major forms. Functional investigations indicate type Igamma has greater catalytic activity compared with other variants and isoforms. Finally, all forms of type I show an increased propensity to form intracellular macrostructures compared to type II and these structures appear to be regulated in response to changing intracellular GTP levels. Collectively these data demonstrate that (i) type I does not play a role in early retinal development, (ii) type Igamma has greater activity and (iii) there are differences between type I and type II isoforms. These observations are consistent with the aetiology of retinitis pigmentosa and raise the possibility that programmed expression of specific inosine monophosphate dehydrogenase proteins may have arisen to meet the requirements of the cellular environment. |
Databáze: | OpenAIRE |
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