Localization of UDP-GlcNAc 2-epimerase/ManAc kinase (GNE) in the Golgi complex and the nucleus of mammalian cells
- Friedrich-Baur-Institute, Department of Neurology and Gene Center, Ludwig-Maximilians-University, Genzentrum Muenchen, Feodor-Lynen-Str. 25, 81377 Munich (Germany)
- Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Institut fuer Biochemie und Molekularbiologie, Berlin-Dahlem (Germany)
- The Goldyne-Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem (Israel)
- Department of Neurology, University of Tuebingen, Tuebingen (Germany)
- Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem (Israel)
- Goldyne-Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem (Israel)
The bifunctional enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) is essential for early embryonic development and catalyzes the rate limiting step in sialic acid biosynthesis. Although epimerase and kinase activities have been attributed to GNE, little is known about the regulation, differential expression, and subcellular localization of GNE in vivo. Mutations in GNE cause a rare inherited muscle disorder in humans called hereditary inclusion body myopathy (HIBM). However, the role of GNE in HIBM pathogenesis has not been defined yet. Here, we show that the GNE protein is expressed in various mammalian cells and tissues with highest levels found in cancer cells and liver. In human skeletal muscle, GNE protein is developmentally regulated: high levels are found in immature myoblasts but low levels in mature skeletal muscle. The GNE protein colocalizes with resident proteins of the Golgi compartment in a variety of human cells including muscle. Drug-induced disruption of the Golgi and subsequent recovery reveals co-distribution of GNE along with Golgi-targeted proteins. This subcellular localization of GNE is in good agreement with its established role as the key enzyme of sialic acid biosynthesis, since the sialylation of glycoconjugates takes place in the Golgi complex. Surprisingly, GNE is also detected in the nucleus. Upon nocodazole treatment, GNE redistributes to the cytoplasm suggesting that GNE may act as a nucleocytoplasmic shuttling protein. A regulatory role for GNE shifting between the nuclear and the Golgi compartment is proposed. Further insight into GNE regulation may promote the understanding of HIBM pathogenesis.
- OSTI ID:
- 20717562
- Journal Information:
- Experimental Cell Research, Vol. 304, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2004.11.010; PII: S0014-4827(04)00681-0; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
Similar Records
Nucleocytoplasmic shuttling of STK16 (PKL12), a Golgi-resident serine/threonine kinase involved in VEGF expression regulation
Biosynthesis of N-glycolyneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool