 |
 Previous Article | Next Article 
Volume 17, Number 10,
Issue of May 15, 1997
pp. 3515-3524
Copyright ©1997 Society for Neuroscience
Modulation of Actin Filament Behavior by GAP-43 (Neuromodulin) Is
Dependent on the Phosphorylation Status of Serine 41, the Protein
Kinase C Site
Received Dec. 19, 1996; revised March 4, 1997; accepted March 5, 1997.
Qin He,
Erik W. Dent, and
Karina F. Meiri
Departments of Pharmacology and Anatomy and Cell Biology, SUNY
Health Science Center, Syracuse, New York 13210
Synthesis of GAP-43 (also known as neuromodulin) in neurons is
induced during axon growth, and high concentrations (estimated between
50 and 100 µM) accumulate in the growth cone. GAP-43 is tightly associated with the growth cone membrane skeleton, the structure that transduces extracellular guidance cues into alterations in morphology by spatially regulating polymerization of actin filaments, thereby causing directional changes in axon growth. GAP-43
cosediments with actin filaments, and its phosphorylation on serine 41 by PKC, too, is spatially regulated so that phosphorylated GAP-43 is
found in areas where growth cones make productive, stable contacts with
other cells. In contrast, unphosphorylated GAP-43, which binds
calmodulin, is always found in parts of the growth cone that are
retracting. Here we have used a cell-free assay to investigate how the
phosphorylation status of GAP-43 affects its interactions with actin
and show that both phosphorylated and unphosphorylated GAP-43 have
different, independent effects on actin filament structure.
Phosphorylated GAP-43 stabilizes long actin filaments
(Kd = 161 nM), and antibodies to phosphorylated GAP-43 inhibit binding of actin to phalloidin, implying
a lateral interaction with filaments. In contrast, unphosphorylated GAP-43 reduces filament length distribution (Kd = 1.2 µM) and increases the critical concentration for
polymerization. Prebinding calmodulin potentiates this effect. The
results show that spatially regulated post-translational modifications
of GAP-43 within the growth cone, which can be regulated in response to extracellular signals, have the ability to directly influence the
structure of the actin cytoskeleton.
Key words:
GAP-43;
neuromodulin;
actin filaments;
growth cones;
capping proteins;
PKC phosphorylation
This article has been cited by other articles:
|
|
|
|
 
R. Gopalakrishna, U. Gundimeda, J. E. Schiffman, and T. H. McNeill
A Direct Redox Regulation of Protein Kinase C Isoenzymes Mediates Oxidant-induced Neuritogenesis in PC12 Cells
J. Biol. Chem.,
May 23, 2008;
283(21):
14430 - 14444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Holahan, K. S. Honegger, N. Tabatadze, and A. Routtenberg
GAP-43 gene expression regulates information storage
Learn. Mem.,
June 6, 2007;
14(6):
407 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Valerio, V. Ghisi, M. Dossena, C. Tonello, A. Giordano, A. Frontini, M. Ferrario, M. Pizzi, P. Spano, M. O. Carruba, et al.
Leptin Increases Axonal Growth Cone Size in Developing Mouse Cortical Neurons by Convergent Signals Inactivating Glycogen Synthase Kinase-3beta
J. Biol. Chem.,
May 5, 2006;
281(18):
12950 - 12958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Lalli and A. Hall
Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex
J. Cell Biol.,
December 5, 2005;
171(5):
857 - 869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yoshida and M. Mishina
Distinct Roles of Calcineurin-Nuclear Factor of Activated T-Cells and Protein Kinase A-cAMP Response Element-Binding Protein Signaling in Presynaptic Differentiation
J. Neurosci.,
March 23, 2005;
25(12):
3067 - 3079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Fischer, F. Sananbenesi, C. Schrick, J. Spiess, and J. Radulovic
Distinct Roles of Hippocampal De Novo Protein Synthesis and Actin Rearrangement in Extinction of Contextual Fear
J. Neurosci.,
February 25, 2004;
24(8):
1962 - 1966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Irwin, S. Chao, L. Goritchenko, A. Horiuchi, P. Greengard, A. C. Nairn, and L. I. Benowitz
Nerve growth factor controls GAP-43 mRNA stability via the phosphoprotein ARPP-19
PNAS,
September 17, 2002;
99(19):
12427 - 12431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Banan, J. Z. Fields, A. Farhadi, D. A. Talmage, L. Zhang, and A. Keshavarzian
The beta 1 Isoform of Protein Kinase C Mediates the Protective Effects of Epidermal Growth Factor on the Dynamic Assembly of F-Actin Cytoskeleton and Normalization of Calcium Homeostasis in Human Colonic Cells
J. Pharmacol. Exp. Ther.,
June 1, 2002;
301(3):
852 - 866.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-Q. Zhou, C. M. Waterman-Storer, and C. S. Cohan
Focal loss of actin bundles causes microtubule redistribution and growth cone turning
J. Cell Biol.,
May 28, 2002;
157(5):
839 - 849.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Shen, S. Mani, S. L. Donovan, J. E. Schwob, and K. F. Meiri
Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System
J. Neurosci.,
January 1, 2002;
22(1):
239 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Andrews, A. D. Munday, C. A. Mitchell, and M. C. Berndt
Interaction of calmodulin with the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex
Blood,
August 1, 2001;
98(3):
681 - 687.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Kabir, A. W. Schaefer, A. Nakhost, W. S. Sossin, and P. Forscher
Protein Kinase C Activation Promotes Microtubule Advance in Neuronal Growth Cones by Increasing Average Microtubule Growth Lifetimes
J. Cell Biol.,
March 5, 2001;
152(5):
1033 - 1044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Laux, K. Fukami, M. Thelen, T. Golub, D. Frey, and P. Caroni
GAP43, MARCKS, and CAP23 Modulate PI(4,5)P2 at Plasmalemmal Rafts, and Regulate Cell Cortex Actin Dynamics through a Common Mechanism
J. Cell Biol.,
June 26, 2000;
149(7):
1455 - 1472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Routtenberg, I. Cantallops, S. Zaffuto, P. Serrano, and U. Namgung
Enhanced learning after genetic overexpression of a brain growth protein
PNAS,
June 20, 2000;
97(13):
7657 - 7662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Lautermilch and N. C. Spitzer
Regulation of Calcineurin by Growth Cone Calcium Waves Controls Neurite Extension
J. Neurosci.,
January 1, 2000;
20(1):
315 - 325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Welnhofer, L. Zhao, and C. S. Cohan
Calcium Influx Alters Actin Bundle Dynamics and Retrograde Flow in Helisoma Growth Cones
J. Neurosci.,
September 15, 1999;
19(18):
7971 - 7982.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Reed, B. Finnerty, and A. P. Albino
Divergent Cellular Differentiation Pathways during the Invasive Stage of Cutaneous Malignant Melanoma Progression
Am. J. Pathol.,
August 1, 1999;
155(2):
549 - 555.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Isbister and T. P. O'Connor
Filopodial Adhesion Does Not Predict Growth Cone Steering Events In Vivo
J. Neurosci.,
April 1, 1999;
19(7):
2589 - 2600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. F. Meiri, J. L. Saffell, F. S. Walsh, and P. Doherty
Neurite Outgrowth Stimulated by Neural Cell Adhesion Molecules Requires Growth-Associated Protein-43 (GAP-43) Function and Is Associated with GAP-43 Phosphorylation in Growth Cones
J. Neurosci.,
December 15, 1998;
18(24):
10429 - 10437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Job and L. Lagnado
Calcium and Protein Kinase C Regulate the Actin Cytoskeleton in the Synaptic Terminal of Retinal Bipolar Cells
J. Cell Biol.,
December 14, 1998;
143(6):
1661 - 1672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. J. Aarts, L. H. Schrama, W. J. Hage, J. L. Bos, W. H. Gispen, and P. Schotman
B-50/GAP-43-induced Formation of Filopodia Depends on Rho-GTPase
Mol. Biol. Cell,
June 1, 1998;
9(6):
1279 - 1292.
[Abstract]
[Full Text]
|
|
|
|
