Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver.
Abstract
A small portion of cellular glycogen is transported to and degraded in lysosomes by
acid α-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported
to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking
to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in
GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To
further determine whether Stbd1 participates in glycogen transport to lysosomes, we
generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen
accumulation in skeletal and cardiac muscles was not affected, but glycogen content
in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared
with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was
suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double
knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out
mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another
mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal
starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that
Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the
N-terminal transmembrane region and the C-terminal CBM20 domain are critical for this
function.
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https://hdl.handle.net/10161/12529Published Version (Please cite this version)
10.1074/jbc.C116.741397Publication Info
Sun, Tao; Yi, Haiqing; Yang, Chunyu; Kishnani, Priya S; & Sun, Baodong (2016). Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport
to Lysosomes in Liver. J Biol Chem, 291(32). pp. 16479-16484. 10.1074/jbc.C116.741397. Retrieved from https://hdl.handle.net/10161/12529.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Priya Sunil Kishnani
Chen Family Distinguished Professor of Pediatrics
RESEARCH INTERESTS A multidisciplinary approach to care of individuals with genetic
disorders in conjunction with clinical and bench research that contributes to: 1)
An understanding of the natural history and delineation of long term complications
of genetic disorders with a special focus on liver Glycogen storage disorders, lysosomal
disorders witha special focus on Pompe disease, Down syndrome and hypophosphatasia2)
The development of new therapies for genetic d
Baodong Sun
Associate Professor in Pediatrics
My overall research interests are finding effective treatment for human glycogen storage
diseases (GSDs) and other inherited metabolic disorders. My current research focuses
on identification of novel therapeutic targets and development of effective therapies
for GSD II (Pompe disease), GSD III (Cori disease), and GSD IV (Andersen disease)
using cellular and animal disease models. The main therapeutic approaches we are using
in our pre-clinical studie
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