title: Cellular and ultra structural evidence for cytoskeletal localization of prolyl endopeptidase-like protein in neurons.
abstract: The biochemical properties and subcellular localization of prolyl endopeptidase (PREP) in brain are well characterized and its implications in the realization of cognitive processes and in the pathogenesis of neurodegenerative disorders are a matter of intensive investigation. In contrast, very little is known about its homolog, the PREP-like protein (PREPL). In order to obtain initial hints about the involvement of PREPL in physiological processes, a differential proteomic screen was performed with human skin fibroblasts from controls and patients with PREPL deficiency (hypotonia-cystinuria syndrome). The majority of affected proteins represented cytoskeletal proteins, including caldesmon, tropomyosin α3 chain, lamin A, β-actin, γ-actin, vimentin and zyxin. Therefore, the analysis of PREPL subcellular localization by confocal laser scanning and electron microscopy in mouse neurons was focused on the cytoskeleton. The co-localization of PREPL with cytoskeletal marker proteins such as β-actin and microtubulin-associated protein-2 was observed, in addition to the presence of PREPL within Golgi apparatus and growth cones. In the mouse brain, PREPL is neuronally expressed and highly abundant in neocortex, substantia nigra and locus coeruleus. This mirrors to some extent the distribution pattern of PREP and points toward redundant functions of both proteins. In the human neocortex, PREPL immunostaining was found in the cytoplasm and in neuropil, in particular of layer V pyramidal neurons. This staining was reduced in the neocortex of Alzheimer's disease (AD) patients. Moreover, in AD brains, PREPL immunoreactivity was observed in the nucleus and in varicose neuritic processes. Our data indicate physiological functions of PREPL associated with the cytoskeleton, which may be affected under conditions of cytoskeletal degeneration.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, 04109 Leipzig, Jahnallee 59, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Morawski
authors.forename: K
authors.initials: K
authors.lastname: Nuytens
authors.forename: T
authors.initials: T
authors.lastname: Juhasz
authors.forename: U
authors.initials: U
authors.lastname: Zeitschel
authors.forename: G
authors.initials: G
authors.lastname: Seeger
authors.forename: E
authors.initials: E
authors.lastname: Waelkens
authors.forename: L
authors.initials: L
authors.lastname: Regal
authors.forename: I
authors.initials: I
authors.lastname: Schulz
authors.forename: T
authors.initials: T
authors.lastname: Arendt
authors.forename: Z
authors.initials: Z
authors.lastname: Szeltner
authors.forename: J
authors.initials: J
authors.lastname: Creemers
authors.forename: S
authors.initials: S
authors.lastname: Rossner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002891:Chromosomes, Human, Pair 21 / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000378:metabolism; D003555:Cystinuria / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008607:Intellectual Disability / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D051379:Mice; D028361:Mitochondrial Diseases / Q000378:metabolism; D009123:Muscle Hypotonia / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D000085822:Prolyl Oligopeptidases; D040901:Proteomics; D017966:Pyramidal Cells / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases