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EXT1 & EXT2 proteins and heparan sulfate biosynthesis
Abstract 2005 MHE Conference
Maria Wilén1, Marta Busse1 and Marion Kusche-Gullberg1,2
1 Department of Medical Biochemistry and Microbiology,
University of Uppsala, Uppsala, Sweden and
2Department of Biomedicine, Division of Physiology,
University of Bergen, Norway
Heparan sulfate is a complex polysaccharide that plays an important role in several cellular processes,
including normal fetal development, wound healing and inflammation. Defects in enzymes involved in
heparan sulfate synthesis result in different abnormalities including abnormal skeletal and kidney
development. Heparan sulfate is elongated by the alternating transfer of glucuronic acid (GlcA) and
N-acetylglucosamine (GlcNAc) units. Concomitant with elongation, the polymer is modified through a
series of reactions that requires the action of several different enzymes. The extent of these
reactions varies, giving rise to heparan sulfate chains with different structural properties.
The chain elongation reaction has been ascribed to a hetero-oligomeric complex of EXT1 and EXT2.
Mutations in either EXT1 or EXT2 have been linked to the human disorder, hereditary multiple
exostoses (HME), characterized by the formation of cartilage-capped bony outgrowths at the end of
the long bones.
The individual functions of EXT1 and EXT2 in heparan sulfate chain elongation are currently
unknown. EXT1 alone has the capacity to elongate heparan sulfate chains in vitro. Furthermore,
reduced EXT1 expression levels results in the formation of heparan sulfate chains that are shorter
than those normally synthesized. The level of EXT2 protein modifies the catalytic properties of EXT1
but the role of EXT2 in heparan sulfate chain elongation is not clear.
To evaluate the effect of EXT2-mutations on heparan sulfate structure, we have generated
transgenic mice with a general and constitutive tissue expression of wild-type or mutated EXT2. To
understand the individual roles of EXT1 and EXT2, we have overexpressed the proteins or reduced
their levels in mammalian cell systems and studied the effects of these manipulations on heparan
sulfate structure.
Abstract 2005 MHE Conference
Maria Wilén1, Marta Busse1 and Marion Kusche-Gullberg1,2
1 Department of Medical Biochemistry and Microbiology,
University of Uppsala, Uppsala, Sweden and
2Department of Biomedicine, Division of Physiology,
University of Bergen, Norway
Heparan sulfate is a complex polysaccharide that plays an important role in several cellular processes,
including normal fetal development, wound healing and inflammation. Defects in enzymes involved in
heparan sulfate synthesis result in different abnormalities including abnormal skeletal and kidney
development. Heparan sulfate is elongated by the alternating transfer of glucuronic acid (GlcA) and
N-acetylglucosamine (GlcNAc) units. Concomitant with elongation, the polymer is modified through a
series of reactions that requires the action of several different enzymes. The extent of these
reactions varies, giving rise to heparan sulfate chains with different structural properties.
The chain elongation reaction has been ascribed to a hetero-oligomeric complex of EXT1 and EXT2.
Mutations in either EXT1 or EXT2 have been linked to the human disorder, hereditary multiple
exostoses (HME), characterized by the formation of cartilage-capped bony outgrowths at the end of
the long bones.
The individual functions of EXT1 and EXT2 in heparan sulfate chain elongation are currently
unknown. EXT1 alone has the capacity to elongate heparan sulfate chains in vitro. Furthermore,
reduced EXT1 expression levels results in the formation of heparan sulfate chains that are shorter
than those normally synthesized. The level of EXT2 protein modifies the catalytic properties of EXT1
but the role of EXT2 in heparan sulfate chain elongation is not clear.
To evaluate the effect of EXT2-mutations on heparan sulfate structure, we have generated
transgenic mice with a general and constitutive tissue expression of wild-type or mutated EXT2. To
understand the individual roles of EXT1 and EXT2, we have overexpressed the proteins or reduced
their levels in mammalian cell systems and studied the effects of these manipulations on heparan
sulfate structure.
Research authored by Dr. Kushe-Gullberg
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
Dr. Kusche-Gullberg's research
Press Release 11 / 02 / 07
Contribution of EXT1, EXT2, and EXTL3 to Heparan Sulfate Chain Elongation*
J. Biol. Chem., Vol. 282, Issue 45, 32802-32810, November 9, 2007
To read journal abstract or full publication
Marta Busse, Almir Feta, Jenny Presto, Maria Wilén, Mona Grønning, Lena Kjellén, and
Marion Kusche-Gullberg
From the Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen,
Norway and the Department of Medical Biochemistry and Microbiology, University of Uppsala, BMC
Box 582, SE-751 23 Uppsala, Sweden
Dr. Marion Kusche-Gullberg presented her research findings during the first MHE Research
Conference held in 2002 and again at the last conference held 2005 and look forward to having the
honor of having her present her research again at the Third International MHE Research Conference
to be held July 8-11, 2009. Our Foundation would like to thank Marion and all of the research
investigators working with her for all of her research efforts over the past many years and the
insights they have on Multiple Hereditary Exostoses.
Contribution of EXT1, EXT2, and EXTL3 to Heparan Sulfate Chain Elongation*
J. Biol. Chem., Vol. 282, Issue 45, 32802-32810, November 9, 2007
To read journal abstract or full publication
Marta Busse, Almir Feta, Jenny Presto, Maria Wilén, Mona Grønning, Lena Kjellén, and
Marion Kusche-Gullberg
From the Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen,
Norway and the Department of Medical Biochemistry and Microbiology, University of Uppsala, BMC
Box 582, SE-751 23 Uppsala, Sweden
Dr. Marion Kusche-Gullberg presented her research findings during the first MHE Research
Conference held in 2002 and again at the last conference held 2005 and look forward to having the
honor of having her present her research again at the Third International MHE Research Conference
to be held July 8-11, 2009. Our Foundation would like to thank Marion and all of the research
investigators working with her for all of her research efforts over the past many years and the
insights they have on Multiple Hereditary Exostoses.
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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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