Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus

Abstract Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloprotea...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nina Westphal, Gabriele Loers, David Lutz, Thomas Theis, Ralf Kleene, Melitta Schachner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/339e825c41804024ad37e70aabcd6f90
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:339e825c41804024ad37e70aabcd6f90
record_format	dspace
spelling	oai:doaj.org-article:339e825c41804024ad37e70aabcd6f902021-12-02T16:06:45ZGeneration and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus10.1038/s41598-017-09468-82045-2322https://doaj.org/article/339e825c41804024ad37e70aabcd6f902017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09468-8https://doaj.org/toc/2045-2322Abstract Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane. These treatments lead to activation of the fibroblast growth factor (FGF) receptor, phospholipase C (PLC), protein kinase C (PKC) and phosphoinositide-3-kinase (PI3K), and subsequently to phosphorylation of MARCKS. Moreover, the NCAM antibody triggers calmodulin-dependent activation of nitric oxide synthase, nitric oxide (NO) production, NO-dependent S-nitrosylation of matrix metalloprotease 9 (MMP9) as well as activation of matrix metalloprotease 2 (MMP2) and MMP9, whereas the ED peptide activates phospholipase D (PLD) and MMP2, but not MMP9. These results indicate that the nuclear PSA-carrying NCAM fragment is generated by distinct and functionally defined signal transducing mechanisms.Nina WestphalGabriele LoersDavid LutzThomas TheisRalf KleeneMelitta SchachnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nina Westphal Gabriele Loers David Lutz Thomas Theis Ralf Kleene Melitta Schachner Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
description	Abstract Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane. These treatments lead to activation of the fibroblast growth factor (FGF) receptor, phospholipase C (PLC), protein kinase C (PKC) and phosphoinositide-3-kinase (PI3K), and subsequently to phosphorylation of MARCKS. Moreover, the NCAM antibody triggers calmodulin-dependent activation of nitric oxide synthase, nitric oxide (NO) production, NO-dependent S-nitrosylation of matrix metalloprotease 9 (MMP9) as well as activation of matrix metalloprotease 2 (MMP2) and MMP9, whereas the ED peptide activates phospholipase D (PLD) and MMP2, but not MMP9. These results indicate that the nuclear PSA-carrying NCAM fragment is generated by distinct and functionally defined signal transducing mechanisms.
format	article
author	Nina Westphal Gabriele Loers David Lutz Thomas Theis Ralf Kleene Melitta Schachner
author_facet	Nina Westphal Gabriele Loers David Lutz Thomas Theis Ralf Kleene Melitta Schachner
author_sort	Nina Westphal
title	Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
title_short	Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
title_full	Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
title_fullStr	Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
title_full_unstemmed	Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
title_sort	generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule ncam to the cell nucleus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/339e825c41804024ad37e70aabcd6f90
work_keys_str_mv	AT ninawestphal generationandintracellulartraffickingofapolysialicacidcarryingfragmentoftheneuralcelladhesionmoleculencamtothecellnucleus AT gabrieleloers generationandintracellulartraffickingofapolysialicacidcarryingfragmentoftheneuralcelladhesionmoleculencamtothecellnucleus AT davidlutz generationandintracellulartraffickingofapolysialicacidcarryingfragmentoftheneuralcelladhesionmoleculencamtothecellnucleus AT thomastheis generationandintracellulartraffickingofapolysialicacidcarryingfragmentoftheneuralcelladhesionmoleculencamtothecellnucleus AT ralfkleene generationandintracellulartraffickingofapolysialicacidcarryingfragmentoftheneuralcelladhesionmoleculencamtothecellnucleus AT melittaschachner generationandintracellulartraffickingofapolysialicacidcarryingfragmentoftheneuralcelladhesionmoleculencamtothecellnucleus
_version_	1718384834523430912

Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus

Ejemplares similares