Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5).
Spinophilin is a protein that binds to protein phosphatase-1 and actin and modulates excitatory synaptic transmission and dendritic spine morphology. We have identified three sites phosphorylated by ERK2 (Ser-15 and Ser-205) and cyclin-dependent PK 5 (Cdk5) (Ser-17), within the actin-binding domain of spinophilin. Cdk5 and ERK2 both phosphorylated spinophilin in intact cells. However, in vitro, phosphorylation by ERK2, but not by Cdk5, was able to modulate the ability of spinophilin to bind to and bundle actin filaments. In neurons and HEK293 cells expressing GFP-tagged variants of spinophilin, imaging studies demonstrated that introduction of a phospho-site mimic (Ser-15 to glutamate) was associated with increased filopodial density. These results support a role for spinophilin phosphorylation by ERK2 in the regulation of spine morphogenesis.
Futter
Marie
M
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.
Uematsu
Ken
K
Bullock
Stewart A
SA
Kim
Yong
Y
Hemmings
Hugh C
HC
Nishi
Akinori
A
Greengard
Paul
P
Nairn
Angus C
AC
D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010449:Peptide Mapping; D010766:Phosphorylation; D011485:Protein Binding; D000099273:Neurabins
D000199:Actins; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1; D009419:Nerve Tissue Proteins; D000099273:Neurabins; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse
J Neurochem. 1999 May;72(5):2015-21
10217279
Nat Neurosci. 1998 Nov;1(7):602-9
10196568
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11062-8
11572969
Learn Mem. 2001 Sep-Oct;8(5):272-8
11584074
Mol Cell Biol. 2002 Jul;22(13):4690-701
12052877
Neuromolecular Med. 2002;2(1):61-9
12230305
Nature. 2002 Dec 19-26;420(6917):788-94
12490942
J Biol Chem. 2003 Jan 10;278(2):1186-94
12417592
Neuroscience. 2003;116(1):19-22
12535933
Neuron. 2003 Jan 23;37(2):263-74
12546821
J Neurosci. 2003 Feb 15;23(4):1189-97
12598607
J Cell Biol. 2003 Dec 22;163(6):1313-26
14691139
Brain Res Mol Brain Res. 2004 May 19;124(2):105-13
15135218
J Neurochem. 2004 Jul;90(2):317-24
15228588
J Neurochem. 2004 Sep;90(5):1094-103
15312165
Neuron. 2004 Oct 14;44(2):321-34
15473970
J Neurochem. 1993 Nov;61(5):1626-33
7693864
J Neurochem. 1995 Sep;65(3):1282-9
7643105
J Neurosci. 1996 May 1;16(9):2983-94
8622128
J Neurosci. 1996 Sep 1;16(17):5425-36
8757255
Neuron. 1997 Jun;18(6):913-24
9208859
Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9956-61
9275233
J Biol Chem. 1998 Feb 6;273(6):3470-5
9452470
J Neurosci. 1998 May 1;18(9):3480-7
9547255
Neuron. 1998 May;20(5):847-54
9620690
J Neurosci. 1998 Dec 1;18(23):9835-44
9822742
J Neurosci. 1998 Dec 1;18(23):10037-44
9822758
Nat Neurosci. 1999 Jan;2(1):13-7
10195174
Biochemistry. 1999 Apr 6;38(14):4365-73
10194355
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13438-43
10557339
Nature. 1999 Dec 9;402(6762):669-71
10604473
Nature. 2000 Apr 20;404(6780):876-81
10786794
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9287-92
10922077
Nat Neurosci. 2000 Sep;3(9):887-94
10966619
Hippocampus. 2000;10(5):527-41
11075823
Nat Neurosci. 2001 Feb;4(2):151-8
11175875
Nature. 2001 Mar 15;410(6826):376-80
11268215