GDE transmembrane ecto-enzymes : novel signaling functions through GPI-anchor cleavage

Veen, T.P.M. van

Te studies described in this thesis focus on the role of GDE2 and GDE3 on GPI-anchor
hydrolysis to increase our understanding of their physiological functions. Chapter 1
is a general introduction giving an overview of the current knowledge and progress in
GPI-anchored bio-synthesis and signaling, together with an overview of the developing
understanding of the mammalian GDPD protein family. Chapter 2 identifies GDE3 as the
first mammalian GPI-specific PLC that selectively cleaves and releases the urokinase receptor
(uPAR) from the membrane. By doing so, GDE3 negatively regulates uPAR signaling in breast
cancer cells. Its closest family member, GDE2, associates with a positive clinical outcome
in neuroblastoma, a childhood disease characterized by defective neuronal diﬀerentiation.
The molecular mechanism involving neuronal diﬀerentiation through selective release of
Glypican 6 by GDE2 is presented in Chapter 3. Addendum...Show moreTe studies described in this thesis focus on the role of GDE2 and GDE3 on GPI-anchor
hydrolysis to increase our understanding of their physiological functions. Chapter 1
is a general introduction giving an overview of the current knowledge and progress in
GPI-anchored bio-synthesis and signaling, together with an overview of the developing
understanding of the mammalian GDPD protein family. Chapter 2 identifies GDE3 as the
first mammalian GPI-specific PLC that selectively cleaves and releases the urokinase receptor
(uPAR) from the membrane. By doing so, GDE3 negatively regulates uPAR signaling in breast
cancer cells. Its closest family member, GDE2, associates with a positive clinical outcome
in neuroblastoma, a childhood disease characterized by defective neuronal diﬀerentiation.
The molecular mechanism involving neuronal diﬀerentiation through selective release of
Glypican 6 by GDE2 is presented in Chapter 3. Addendum Chapter 3 comments on the
release of GPI-anchored proteins during neuronal diﬀerentiation. Next, Chapter 4 explores
the involvement of GDE2 in zebrafish development and describes a potential role for GDE2
in the development of the pancreas. Chapter 5 compares the enzymatic activity towards
specifc GPI-anchored proteins and localization of GDE2 and GDE3. In Chapter 6, the results
presented in this thesis are summarized and discussed.Show less

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GDE transmembrane ecto-enzymes : novel signaling functions through GPI-anchor cleavage

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