Research:
Protein N-glycosylation in Growth and Development
Modification of proteins with N-glycans (N-glycosylation) is critical
for a number of developmental and physiological processes in all eukaryotes.
Our work focuses on the role of protein N-glycosylation in cell function
and tissue development. Protein N-glycosylation is initiated by the
ALG7 gene that functions at the first committed step in the synthesis
of the lipid-linked oligosaccharide (LLO) precursor and is a key regulator
LLO abundance in vivo. To determine how ALG7 regulates cell function
we have examined the consequences of inappropriate expression of ALG7
in the yeast Saccharomyces cerevisiae. Yeast cells with disregulated
ALG7 display perturbation of a number of signaling and metabolic pathways.
To identify the downstream targets of ALG7, we have generated a mutant
alg7 strain with a genomic hypomorphic allele of ALG7. This mutant
is being used in a genetic screen to search for factor(s) affected
by inappropriate protein N-glycosylation.
To further characterize the role of ALG7 in mammalian development, we
are using the mouse submandibular gland (SMG) as a model. In the SMG,
ALG7 is highly expressed during periods of active cell proliferation
and it is downregulated with cellular differentiation. To determine how
changes in ALG7 expression guide SMG development, we have focused on
the relationships between ALG7 and E-cadherin, an N-glycosylated cell-cell
adhesion receptor that plays pivotal roles in epithelial tissue development.
We have shown that changes in ALG7 expression modulate the N-glycosylation
status of E-cadherin and its adhesion dynamics during morphogenesis and
differentiation. Our current studies focus on characterizing the roles
of E-cadherin N-glycans in cell-cell adhesion during SMG organogenesis
using perturbation approaches in SMG explant cultures ex vivo and in
transgenic mice in vivo.
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Maria A. Kukuruzinska
Professor
Ph.D. The Johns Hopkins University, 1983
Postdoctoral Training Massachusetts Institute of Technology, 1984-1988
Address:
715 Albany Street, Evans 4, room 428,
Boston, MA 02118-2394
Tel:617/638-4859
mkukuruz@bu.edu
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