Neurons switch from non-neuronal enolase to neuron-specific enolase during differentiation

The enolase (EC 4.2.1.11) isoenzymes, neuron-specific enolase (NSE, gamma gamma) and non-neuronal enolase (NNE, alpha alpha), are markers for neurons and glia, respectively, in adult mammalian brain. In developing fetal and early postnatal brain, levels of non-neuronal enolase (NNE) are high. Neuron-specific enolase (NSE) appears only after neurogenesis begins in a given region and only slowly attains adult levels. Immunocytochemistry in developing rat and rhesus monkey brain reveals that proliferative zones that give rise to neurons are NNE(+). Thus, nerve cells must undergo a switch from NNE to NSE. In addition, study of neurons in cerebellum and neocortex reveals that they are NNE(+) during migration and only become NSE(+) in their final location, presumably after making full synaptic connections. Such migrating cells may contain hybrid enolase (alpha gamma) and some (e.g. cerebellar stellate/basket cells) may not completely switch over to NSE even in the adult. Neuron-specific enolase is not only a specific molecular marker for mature nerve cells, but is closely correlated to the differentiated state.

[1]  B. Moore.  Chemistry and biology of two proteins, S-100 and 14-3-2, specific to the nervous system. , 1972, International review of neurobiology.

[2]  H. Harris,et al.  Human enolase isozymes: electrophoretic and biochemical evidence for three loci , 1976, Annals of human genetics.

[3]  J. Barker,et al.  Localization of neuron-specific enolase in mouse spinal neurons grown in tissue culture , 1980, Brain Research.

[4]  P. Rakic,et al.  Arrested proliferation of radial glial cells during midgestation in rhesus monkey , 1979, Nature.

[5]  P. Rakić,et al.  Timing of major ontogenetic events in the visual cortex of the rhesus monkey. , 1975, UCLA forum in medical sciences.

[6]  D. McFarlin,et al.  Protein A-peroxidase: a valluable tool for the localization of antigens. , 1977, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[7]  F. Goodwin,et al.  STRUCTURAL AND IMMUNOLOGICAL PROPERTIES OF NEURON SPECIFIC PROTEIN (NSP) FROM RAT, CAT AND HUMAN BRAIN: COMPARISON TO BOVINE 14‐3‐2 , 1977, Journal of neurochemistry.

[8]  F. Goodwin,et al.  Brain endolases as specific markers of neuronal and glial cells. , 1978, Science.

[9]  P. Marangos,et al.  Immunological studies of a nerve specific protein. , 1975, Archives of biochemistry and biophysics.

[10]  D. Reis,et al.  Immunocytochemical localization of nervous system specific protein (NSP-R) in rat brain , 1976, Brain Research.

[11]  E. Giblett,et al.  Enolase: human tissue distribution and evidence for three different loci * , 1976, Annals of human genetics.

[12]  P. Rakić.  Neurons in Rhesus Monkey Visual Cortex: Systematic Relation between Time of Origin and Eventual Disposition , 1974, Science.

[13]  M. Jacobson.  Histogenesis and Morphogenesis of the Central Nervous System , 1978 .

[14]  D. Schmechel,et al.  The neurobiology of the brain enolases. , 1980, Essays in neurochemistry and neuropharmacology.

[15]  D. Schmechel,et al.  Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells , 1978, Nature.

[16]  B. Moore,et al.  REGIONAL CHANGES IN CNS LEVELS OF THE S‐100 AND 14‐3‐2 PROTEINS DURING DEVELOPMENT AND AGING OF THE MOUSE 1 , 1972, Journal of neurochemistry.

[17]  D. Luk,et al.  Isolation and characterization of the nervous system-specific protein 14-3-2 from rat brain. Purification, subunit composition, and comparison to the beef brain protein. , 1975, The Journal of biological chemistry.

[18]  F. Goodwin,et al.  Neuronal, non-neuronal and hybrid forms of enolase in brain: Structural, immunological and functional comparisons , 1978, Brain Research.

[19]  W. Rutter,et al.  Multiple forms of fructose diphosphate aldolase in mammalian tissues. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Rider,et al.  Enolase isoenzymes in rat tissues. Electrophoretic, chromatographic, immunological and kinetic properties. , 1974, Biochimica et biophysica acta.

[21]  F. Goodwin,et al.  FUNCTIONAL PROPERTIES OF NEURONAL AND GLIAL ISOENZYMES OF BRAIN ENOLASE , 1978, Journal of neurochemistry.

[22]  P. Rakić.  Kinetics of proliferation and latency between final cell division and onset of differentiation of cerebellar stellate and basket neurons , 1973, The Journal of comparative neurology.

[23]  W. Rutter,et al.  Distribution of fructose diphosphate aldolase variants in biological systems. , 1969, Biochemistry.

[24]  W. Cowan,et al.  Changes in the concentrations of the two brain specific proteins, s-100 and 14-3-2, during the development of the avian optic tectum. , 1970, Brain research.

[25]  P. Rakić.  Local circuit neurons. , 1975, Neurosciences Research Program bulletin.

[26]  P. Rakić,et al.  Neuron‐glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electonmicroscopic study in Macacus rhesus , 1971, The Journal of comparative neurology.

[27]  I. Kostović,et al.  The development of synapses in cerebral cortex of the human fetus. , 1973, Brain research.

[28]  E. Adamson,et al.  Enolase isoenzymes as markers of differentiation in teratocarcinoma cells and normal tissues of mouse. , 1978, Developmental biology.

[29]  F. Goodwin,et al.  Neuron specific protein (NSP) in neuroblastoma cells: Relation to differentiation , 1978, Brain Research.

[30]  E. Bock,et al.  Demonstration of Enolase Activity Connected to the Brain‐Specific Protein 14‐3‐2 , 1975 .

[31]  E. Bock.  NERVOUS SYSTEM SPECIFIC PROTEINS , 1978, Scandinavian journal of immunology. Supplement.

[32]  F. Goodwin,et al.  MEASUREMENT OF NEURON‐SPECIFIC (NSE) AND NON‐NEURONAL (NNE) ISOENZYMES OF ENOLASE IN RAT, MONKEY AND HUMAN NERVOUS TISSUE , 1979, Journal of neurochemistry.

[33]  C. Rider,et al.  Evidence for a new form of enolase in rat brain. , 1975, Biochemical and biophysical research communications.

[34]  E. Bock,et al.  THE NATURE OF THE TWO PROTEINS OF BRAIN SPECIFIC ANTIGEN 14‐3‐2 , 1978, Journal of neurochemistry.

[35]  F. Goodwin,et al.  Developmental profile of neuron-specific (NSE) and non-neuronal (NNE) enolase , 1980, Brain Research.

[36]  A. Rockel,et al.  Observations on the fine structure of the central nucleus of the inferior colliculus of the cat , 1973, The Journal of comparative neurology.