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Publication year
2009Source
Cerebellum, 8, 2, (2009), pp. 80-8ISSN
Publication type
Article / Letter to editor
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Organization
Cell Biology (UMC)
Neurology
Journal title
Cerebellum
Volume
vol. 8
Issue
iss. 2
Page start
p. 80
Page end
p. 8
Subject
DCN 1: Perception and Action; IGMD 8: Mitochondrial medicine; NCMLS 4: Energy and redox metabolism; NCMLS 5: Membrane transport and intracellular motility; NCMLS 7: Chemical and physical biology; ONCOL 3: Translational researchAbstract
Protein tyrosine phosphatases (PTPs) are central players in many different cellular processes and their aberrant activity is associated with multiple human pathologies. In this review, we present current knowledge on the PTPRR subfamily of classical PTPs that is expressed in neuronal cells and comprises receptor-type (PTPBR7, PTP-SL) as well as cytosolic (PTPPBSgamma-37, PTPPBSgamma-42) isoforms. The two receptor-type isoforms PTPBR7 and PTP-SL both localize in late endosomes and the Golgi area. PTPBR7, however, is additionally localized at the cell surface and on early endosomes. During cerebellar maturation, PTPBR7 expression in developing Purkinje cells ceases and is replaced by PTP-SL expression in the mature Purkinje cells. All PTPRR isoforms contain a kinase interacting motif that makes them mitogen-activated protein kinase phosphatases. The distinct subcellular localization of the different PTPRR isoforms may reflect differential roles in growth-factor-induced MAPK-mediated retrograde signaling cascades. Studies in PTPRR-deficient mice established that PTPRR isoforms are physiological regulators of MAPK phosphorylation levels. Surprisingly, PTPRR-deficient mice display defects in motor coordination and balancing skills, while cerebellar morphological abnormalities, which are often encountered in ataxic mouse models, are absent. This is reminiscent of the phenotype observed in a handful of mouse mutants that have alterations in cerebellar calcium ion homeostasis. Elucidation of the molecular mechanisms by which PTPRR deficiency imposes impairment of cerebellar neurons and motor coordination may provide candidate molecules for hereditary cerebellar ataxias that still await identification of the corresponding disease genes.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122523]
- Faculty of Medical Sciences [90373]
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