Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses

Jenny U. Johansson, Lena Lilja, Xiao Liang Chen, Haruhiro Higashida, Björn Meister, Mami Noda, Zhen Guo Zhong, Shigeru Yokoyama, Per Olof Berggren, Christina Bark

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cyclin-dependent kinase 5 (Cdk5) has emerged as a key coordinator of cell signaling in neurite outgrowth. Cdk5 needs to associate with one of the regulatory proteins p35 or p39 to be an active enzyme. To investigate if Cdk5 plays a role in the establishment of functional synapses, we have characterized the expression of Cdk5, p35, and p39 in the neuroblastoma-glioma cell line NG108-15, and recorded postsynaptic activity in myotubes in response to presynaptic overexpression of Cdk5, p35, and p39. Endogenous Cdk5 and p35 protein levels increased with cellular differentiation and preferentially distributed to soluble pools, whereas the level of p39 protein remained low and primarily was present in membrane and cytoskeletal fractions. Transient transfection of a dominant-negative mutant of Cdk5 in NG108-15 cells and subsequent culturing on differentiating muscle cells resulted in a significant reduction in synaptic activity, as measured by postsynaptic miniature endplate potentials (mEPPs). Overexpression of either Cdk5/p35 or Cdk5/p39 resulted in a substantial increase in synaptic structures that displayed postsynaptic activities, as well as mEPP frequency. These findings demonstrate that Cdk5, p35, and p39 are endogenously expressed in NG108-15 cells, exhibit distinct subcellular localizations, and that both Cdk5/p35 and Cdk5/p39 are central in formation of functional synapses.

Original languageEnglish
Pages (from-to)215-227
Number of pages13
JournalMolecular Brain Research
Volume138
Issue number2
DOIs
Publication statusPublished - Aug 18 2005
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase 5
Synapses
Miniature Postsynaptic Potentials
Proteins
Skeletal Muscle Fibers
Neuroblastoma
Glioma
Muscle Cells
Transfection

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses. / Johansson, Jenny U.; Lilja, Lena; Chen, Xiao Liang; Higashida, Haruhiro; Meister, Björn; Noda, Mami; Zhong, Zhen Guo; Yokoyama, Shigeru; Berggren, Per Olof; Bark, Christina.

In: Molecular Brain Research, Vol. 138, No. 2, 18.08.2005, p. 215-227.

Research output: Contribution to journalArticle

Johansson, JU, Lilja, L, Chen, XL, Higashida, H, Meister, B, Noda, M, Zhong, ZG, Yokoyama, S, Berggren, PO & Bark, C 2005, 'Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses', Molecular Brain Research, vol. 138, no. 2, pp. 215-227. https://doi.org/10.1016/j.molbrainres.2005.04.014
Johansson, Jenny U. ; Lilja, Lena ; Chen, Xiao Liang ; Higashida, Haruhiro ; Meister, Björn ; Noda, Mami ; Zhong, Zhen Guo ; Yokoyama, Shigeru ; Berggren, Per Olof ; Bark, Christina. / Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses. In: Molecular Brain Research. 2005 ; Vol. 138, No. 2. pp. 215-227.
@article{02a773893bb04797adee8a46d43195b7,
title = "Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses",
abstract = "Cyclin-dependent kinase 5 (Cdk5) has emerged as a key coordinator of cell signaling in neurite outgrowth. Cdk5 needs to associate with one of the regulatory proteins p35 or p39 to be an active enzyme. To investigate if Cdk5 plays a role in the establishment of functional synapses, we have characterized the expression of Cdk5, p35, and p39 in the neuroblastoma-glioma cell line NG108-15, and recorded postsynaptic activity in myotubes in response to presynaptic overexpression of Cdk5, p35, and p39. Endogenous Cdk5 and p35 protein levels increased with cellular differentiation and preferentially distributed to soluble pools, whereas the level of p39 protein remained low and primarily was present in membrane and cytoskeletal fractions. Transient transfection of a dominant-negative mutant of Cdk5 in NG108-15 cells and subsequent culturing on differentiating muscle cells resulted in a significant reduction in synaptic activity, as measured by postsynaptic miniature endplate potentials (mEPPs). Overexpression of either Cdk5/p35 or Cdk5/p39 resulted in a substantial increase in synaptic structures that displayed postsynaptic activities, as well as mEPP frequency. These findings demonstrate that Cdk5, p35, and p39 are endogenously expressed in NG108-15 cells, exhibit distinct subcellular localizations, and that both Cdk5/p35 and Cdk5/p39 are central in formation of functional synapses.",
author = "Johansson, {Jenny U.} and Lena Lilja and Chen, {Xiao Liang} and Haruhiro Higashida and Bj{\"o}rn Meister and Mami Noda and Zhong, {Zhen Guo} and Shigeru Yokoyama and Berggren, {Per Olof} and Christina Bark",
year = "2005",
month = "8",
day = "18",
doi = "10.1016/j.molbrainres.2005.04.014",
language = "English",
volume = "138",
pages = "215--227",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses

AU - Johansson, Jenny U.

AU - Lilja, Lena

AU - Chen, Xiao Liang

AU - Higashida, Haruhiro

AU - Meister, Björn

AU - Noda, Mami

AU - Zhong, Zhen Guo

AU - Yokoyama, Shigeru

AU - Berggren, Per Olof

AU - Bark, Christina

PY - 2005/8/18

Y1 - 2005/8/18

N2 - Cyclin-dependent kinase 5 (Cdk5) has emerged as a key coordinator of cell signaling in neurite outgrowth. Cdk5 needs to associate with one of the regulatory proteins p35 or p39 to be an active enzyme. To investigate if Cdk5 plays a role in the establishment of functional synapses, we have characterized the expression of Cdk5, p35, and p39 in the neuroblastoma-glioma cell line NG108-15, and recorded postsynaptic activity in myotubes in response to presynaptic overexpression of Cdk5, p35, and p39. Endogenous Cdk5 and p35 protein levels increased with cellular differentiation and preferentially distributed to soluble pools, whereas the level of p39 protein remained low and primarily was present in membrane and cytoskeletal fractions. Transient transfection of a dominant-negative mutant of Cdk5 in NG108-15 cells and subsequent culturing on differentiating muscle cells resulted in a significant reduction in synaptic activity, as measured by postsynaptic miniature endplate potentials (mEPPs). Overexpression of either Cdk5/p35 or Cdk5/p39 resulted in a substantial increase in synaptic structures that displayed postsynaptic activities, as well as mEPP frequency. These findings demonstrate that Cdk5, p35, and p39 are endogenously expressed in NG108-15 cells, exhibit distinct subcellular localizations, and that both Cdk5/p35 and Cdk5/p39 are central in formation of functional synapses.

AB - Cyclin-dependent kinase 5 (Cdk5) has emerged as a key coordinator of cell signaling in neurite outgrowth. Cdk5 needs to associate with one of the regulatory proteins p35 or p39 to be an active enzyme. To investigate if Cdk5 plays a role in the establishment of functional synapses, we have characterized the expression of Cdk5, p35, and p39 in the neuroblastoma-glioma cell line NG108-15, and recorded postsynaptic activity in myotubes in response to presynaptic overexpression of Cdk5, p35, and p39. Endogenous Cdk5 and p35 protein levels increased with cellular differentiation and preferentially distributed to soluble pools, whereas the level of p39 protein remained low and primarily was present in membrane and cytoskeletal fractions. Transient transfection of a dominant-negative mutant of Cdk5 in NG108-15 cells and subsequent culturing on differentiating muscle cells resulted in a significant reduction in synaptic activity, as measured by postsynaptic miniature endplate potentials (mEPPs). Overexpression of either Cdk5/p35 or Cdk5/p39 resulted in a substantial increase in synaptic structures that displayed postsynaptic activities, as well as mEPP frequency. These findings demonstrate that Cdk5, p35, and p39 are endogenously expressed in NG108-15 cells, exhibit distinct subcellular localizations, and that both Cdk5/p35 and Cdk5/p39 are central in formation of functional synapses.

UR - http://www.scopus.com/inward/record.url?scp=23744464518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23744464518&partnerID=8YFLogxK

U2 - 10.1016/j.molbrainres.2005.04.014

DO - 10.1016/j.molbrainres.2005.04.014

M3 - Article

C2 - 15908038

AN - SCOPUS:23744464518

VL - 138

SP - 215

EP - 227

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -