Cellular Distribution and Developmental Expression of AMP-Activated Protein Kinase Isoforms in Mouse Central Nervous System

Authors

  • Ann M. Turnley,

    1. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia*St. Vincents Institute of Medical Research, Fitzroy, Victoria, AustraliaEndocrine-Metabolism Division, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • David Stapleton,

    1. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia*St. Vincents Institute of Medical Research, Fitzroy, Victoria, AustraliaEndocrine-Metabolism Division, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • * Richard J. Mann,

    1. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia*St. Vincents Institute of Medical Research, Fitzroy, Victoria, AustraliaEndocrine-Metabolism Division, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • * Lee A. Witters,

    1. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia*St. Vincents Institute of Medical Research, Fitzroy, Victoria, AustraliaEndocrine-Metabolism Division, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • Bruce E. Kemp,

    1. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia*St. Vincents Institute of Medical Research, Fitzroy, Victoria, AustraliaEndocrine-Metabolism Division, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • and * Perry F. Bartlett

    1. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia*St. Vincents Institute of Medical Research, Fitzroy, Victoria, AustraliaEndocrine-Metabolism Division, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • Lippincott Williams & Wilkins, Inc., Philadelphia

  • The present address of Dr. D. Stapleton is Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, 600 University Ave., Mount Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada.

  • Abbreviations used: AMPK, AMP-activated protein kinase; DAPI, 4′,6-diamidino-2-phenylindole; E, embryonic day; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFAP, glial fibrillary acidic protein; P, postnatal day; PBS, phosphate-buffered saline; SDS, sodium dodecyl sulfate; SSC, saline—sodium citrate.

Address correspondence and reprint requests to Dr. A. M. Turnley at Neurobiology Laboratory, The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria 3050, Australia.

Abstract

Abstract: The mammalian AMP-activated protein kinase is a heterotrimeric serine/threonine protein kinase with multiple isoforms for each subunit (α, β, and γ) and is activated under conditions of metabolic stress. It is widely expressed in many tissues, including the brain, although its expression pattern throughout the CNS is unknown. We show that brain mRNA levels for the α2 and β2 subunits were increased between embryonic days 10 and 14, whereas expression of α1, β1, and γ1 subunits was consistent at all ages examined. Immunostaining revealed a mainly neuronal distribution of all isoforms. The α2 catalytic subunit was highly expressed in neurons and activated astrocytes, whereas the α1 catalytic subunit showed low expression in neuropil. The γ1 noncatalytic subunit was highly expressed by neurons, but not by astrocytes. Expression of the β1 and β2 noncatalytic subunits varied, but some neurons, such as granule cells of olfactory bulb, did not express detectable levels of either β isoform. Preferential nuclear localization of the α2, β1, and γ1 subunits suggests new functions of the AMP-activated protein kinase, and the different expression patterns and cellular localization between the two catalytic subunits α1 and α2 point to different physiological roles.

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