Nuclear localization of Klotho in brain: An anti-aging protein

Dwight C. German, Ida Khobahy, Johanne Pastor, Makoto Kuro-o, Xinran Liu

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Klotho is a putative age-suppressing gene whose overexpression in mice results in extension of life span. The Klotho gene encodes a single-pass transmembrane protein whose extracellular domain is shed and released into blood, urine, and cerebrospinal fluid, potentially functioning as a humoral factor. The extracellular domain of Klotho has an activity that increases the expression of antioxidant enzymes and confers resistance to oxidative stress in cultured cells and in whole animals. The transmembrane form of the Klotho protein directly binds to multiple fibroblast growth factor receptors and modifies their ligand affinity and specificity. The purpose of the present study was to determine the precise cellular localization of Klotho in the mouse brain. Using light microscopic immunohistochemical methods, we found the highest levels of Klotho immunoreactivity in 2 brain regions: the choroid plexus, and cerebellar Purkinje cells. In the choroid plexus cells, Klotho was found not only on the plasma membrane but also in large amounts near the nuclear membrane. Likewise, in the Purkinje cell Klotho was found throughout the cell including dendrites, axon and soma with large amounts near the nuclear membrane. Using immunoelectron microscopy, we found Klotho in the cell membrane, but the highest concentration was localized in the peripheral portion of the nucleus and the nucleolus in both cell types. This new finding suggests that in addition to Klotho being secreted from cells in brain, it also has a nuclear function.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume33
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Choroid Plexus
Purkinje Cells
Nuclear Envelope
Brain
Proteins
Cell Membrane
Fibroblast Growth Factor Receptors
Immunoelectron Microscopy
Carisoprodol
Dendrites
Life Expectancy
Genes
Axons
Cerebrospinal Fluid
Cultured Cells
Oxidative Stress
Antioxidants
Urine
Ligands
Light

Keywords

  • Choroid plexus
  • Electron microscopy
  • Immunohistochemistry
  • Purkinje cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Nuclear localization of Klotho in brain : An anti-aging protein. / German, Dwight C.; Khobahy, Ida; Pastor, Johanne; Kuro-o, Makoto; Liu, Xinran.

In: Neurobiology of Aging, Vol. 33, No. 7, 07.2012.

Research output: Contribution to journalArticle

German, Dwight C. ; Khobahy, Ida ; Pastor, Johanne ; Kuro-o, Makoto ; Liu, Xinran. / Nuclear localization of Klotho in brain : An anti-aging protein. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 7.
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