Publication: Prosaposin: a protein with
differential sorting and multiple functions
Authors
Carvelli, L. ; Libin, Yuan ; Morales, C.R.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
10.14670/HH-30.647
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info:eu-repo/semantics/article
Description
Abstract
In eukaryotes the delivery of newly
synthesized proteins to their final destination is
dependent on a series of functionally distinct
compartments, including the endoplasmic reticulum and
the Golgi apparatus, which plays a role in posttranslational modification, sorting and distribution of
proteins. Most cargo is sorted within, and exits from, the
trans-Golgi network (TGN). Proteins delivered to
lysosomes include hydrolytic enzymes and nonenzymic
activator proteins. They are directed away from the cell
surface by their binding to mannose-6-phosphate
receptors (MPR). However, in I-cell disease, in which
the MPR pathway is disrupted, the nonenzymic
sphingolipid activator protein, prosaposin, continue to
traffic to lysosomes. This observation led to discovery of
a new lysosomal sorting receptor, sortilin. The targeting
prosaposin to the lysosomes results from the interaction
of its C-terminus with sortilin. Deletion of the Cterminus did not interfere with its secretion, but
abolished its transport to the lysosomes. Mutational
analysis revealed that the first half of the prosaposin Cterminus contains a motif required for its binding to
sortilin and its transport to the lysosomes. Prosaposin
can be also secreted to the extracellular space as
oligomers. Extracellular prosaposin showed to exert a
variety of responses in nervous tissues including the
activation of G protein-coupled receptors and ERK
phosphorylation. Lastly, prosaposin has been found to be
expressed in other fluids of the body such as pancreaticjuice, bile, cerebrospinal fluid, milk and seminal fluid,
indicating that prosaposin is not only a house keeping
lysosomal protein but an essential factor in the
development and maintenance of the nervous systems
and other systems of the body.
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Citation
Histology and Histopathology, vol. 30, nº 6, (2015)
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