scholarly journals Cofilin and Neurodegeneration: New Functions for an Old but Gold Protein

2021 ◽  
Vol 11 (7) ◽  
pp. 954
Author(s):  
Tamara Lapeña-Luzón ◽  
Laura R. Rodríguez ◽  
Vicent Beltran-Beltran ◽  
Noelia Benetó ◽  
Federico V. Pallardó ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Growth Cone ◽  
Mitochondrial Function ◽  
Dendritic Spine ◽  
Cell Biology ◽  
Regulatory Mechanisms ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Neuronal Growth Cone

Cofilin is an actin-binding protein that plays a major role in the regulation of actin dynamics, an essential cellular process. This protein has emerged as a crucial molecule for functions of the nervous system including motility and guidance of the neuronal growth cone, dendritic spine organization, axonal branching, and synaptic signalling. Recently, other important functions in cell biology such as apoptosis or the control of mitochondrial function have been attributed to cofilin. Moreover, novel mechanisms of cofilin function regulation have also been described. The activity of cofilin is controlled by complex regulatory mechanisms, with phosphorylation being the most important, since the addition of a phosphate group to cofilin renders it inactive. Due to its participation in a wide variety of key processes in the cell, cofilin has been related to a great variety of pathologies, among which neurodegenerative diseases have attracted great interest. In this review, we summarized the functions of cofilin and its regulation, emphasizing how defects in these processes have been related to different neurodegenerative diseases.

scholarly journals Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain

2017 ◽  
Vol 217 (1) ◽  
pp. 211-230 ◽  
Author(s):  
Maryam Izadi ◽  
Dirk Schlobinski ◽  
Maria Lahr ◽  
Lukas Schwintzer ◽  
Britta Qualmann ◽  
...  
Keyword(s):  
Actin Filament ◽  
Cell Biology ◽  
Network Formation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Filament Formation ◽  
Uncharacterized Protein ◽  
Dendritic Branching ◽  
Wh2 Domain ◽  
Actin Nucleator

Local actin filament formation powers the development of the signal-receiving arbor of neurons that underlies neuronal network formation. Yet, little is known about the molecules that drive these processes and may functionally connect them to the transient calcium pulses observed in restricted areas in the forming dendritic arbor. Here we demonstrate that Cordon-Bleu (Cobl)–like, an uncharacterized protein suggested to represent a very distantly related, evolutionary ancestor of the actin nucleator Cobl, despite having only a single G-actin–binding Wiskott–Aldrich syndrome protein Homology 2 (WH2) domain, massively promoted the formation of F-actin–rich membrane ruffles of COS-7 cells and of dendritic branches of neurons. Cobl-like hereby integrates WH2 domain functions with those of the F-actin–binding protein Abp1. Cobl-like–mediated dendritic branching is dependent on Abp1 as well as on Ca2+/calmodulin (CaM) signaling and CaM association. Calcium signaling leads to a promotion of complex formation with Cobl-like’s cofactor Abp1. Thus, Ca2+/CaM control of actin dynamics seems to be a much more broadly used principle in cell biology than previously thought.

Use of calcium imaging technologies to dissect mechanisms underlying neuronal growth cone responses to environmental cues

1995 ◽  
Vol 53 ◽  
pp. 804-805
Author(s):  
C.V. Williams ◽  
S.B. Kater
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Local Environment ◽  
Growth Cones ◽  
Neuronal Growth ◽  
Growth Inhibitory ◽  
Direct Growth ◽  
Neuronal Growth Cone ◽  
Mechanical Factors ◽  
Growth Promoting

Since calcium is a key second messenger in both the developmental formation and adult function of the nervous system, the ability to rapidly image changes in this molecule has added greatly to our understanding of how development of the nervous system is regulated. The nervous system is comprised of billions of neurons and glial cells that establish characteristic patterns of connections during development. Neurons extend processes that often must grow long distances to establish appropriate synaptic connections. Neurons perform a pathfinding behavior largely via the highly dynamic behavior of the neuronal growth cone at the distal tip of elongating processes. The motile behavior characteristic of growth cones allows the growth cone to survey the local environment, read local cues and respond to those cues with a change in behavior. A variety of cues are now known to direct growth cones (e.g. electrical activity, depolarization, growth factors, mechanical factors, neurotransmitters, substrate factors). This collection of factors includes both growth promoting and growth inhibitory influences.

Growth cone dynamics of embryonic grasshopper pioneer neurons in situ

1995 ◽  
Vol 53 ◽  
pp. 802-803
Author(s):  
Tim P. O'Connor
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Time Lapse ◽  
Pioneer Neurons ◽  
The Central Nervous System ◽  
Neuronal Growth Cone ◽  
Time Lapse Imaging ◽  
Guidance Information ◽  
Extracellular Environment

During development of the nervous system, neurons extend axons over relatively long distances to contact their targets. A variety of molecules in the extracellular environment are instrumental in guiding a neuronal process. The motile tip of the process, the growth cone, senses and transduces this guidance information, resulting in a local reorganization and consolidation of the cytoskeleton. Although much work has been dedicated to isolating the molecules that guide a neuronal growth cone, relatively little is known about the dynamic processes that occur when a growth cone turns in response to guidance information. Recently, a number of biological systems have been developed that enable time lapse imaging of growth cones as they extend axons in situ. One of these systems is the embryonic grasshopper limb fillet.In the grasshopper embryo, a pair of sibling neurons, named the Til pioneers, are the first neurons to extend axons toward the central nervous system (CNS).

scholarly journals 2P156 F-actin binding proteins, lasp-1, lasp-2, and fascin show different localisation in the neuronal growth cone

2004 ◽  
Vol 44 (supplement) ◽  
pp. S148
Author(s):  
H. Nakagawa ◽  
S. Taguchi ◽  
A.G. Terasaki ◽  
K. Ohashi ◽  
S. Miyamoto
Keyword(s):  
Growth Cone ◽  
Binding Proteins ◽  
Actin Binding ◽  
Neuronal Growth ◽  
Actin Binding Proteins ◽  
Neuronal Growth Cone

scholarly journals Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1525
Author(s):  
Felix Schneider ◽  
Isabell Metz ◽  
Sharof Khudayberdiev ◽  
Marco B. Rust
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Expression Patterns ◽  
Functional Redundancy ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Brain Anatomy ◽  
Compensatory Mechanisms ◽  
Neuron Differentiation ◽  
Associated Proteins

Cyclase-associated proteins (CAPs) are evolutionary-conserved actin-binding proteins with crucial functions in regulating actin dynamics, the spatiotemporally controlled assembly and disassembly of actin filaments (F-actin). Mammals possess two family members (CAP1 and CAP2) with different expression patterns. Unlike most other tissues, both CAPs are expressed in the brain and present in hippocampal neurons. We recently reported crucial roles for CAP1 in growth cone function, neuron differentiation, and neuron connectivity in the mouse brain. Instead, CAP2 controls dendritic spine morphology and synaptic plasticity, and its dysregulation contributes to Alzheimer’s disease pathology. These findings are in line with a model in which CAP1 controls important aspects during neuron differentiation, while CAP2 is relevant in differentiated neurons. We here report CAP2 expression during neuron differentiation and its enrichment in growth cones. We therefore hypothesized that CAP2 is relevant not only in excitatory synapses, but also in differentiating neurons. However, CAP2 inactivation neither impaired growth cone morphology and motility nor neuron differentiation. Moreover, CAP2 mutant mice did not display any obvious changes in brain anatomy. Hence, differently from CAP1, CAP2 was dispensable for neuron differentiation and brain development. Interestingly, overexpression of CAP2 rescued not only growth cone size in CAP1-deficient neurons, but also their morphology and differentiation. Our data provide evidence for functional redundancy of CAP1 and CAP2 in differentiating neurons, and they suggest compensatory mechanisms in single mutant neurons.

CAP1 and cofilin1 cooperate in neuronal actin dynamics, growth cone function and neuron connectivity

2020 ◽  
Author(s):  
Felix Schneider ◽  
Thuy-An Duong ◽  
Isabell Metz ◽  
Jannik Winkelmeier ◽  
Christian A. Hübner ◽  
...  
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Super Resolution ◽  
Growth Cones ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Control Growth ◽  
Cone Function ◽  
And Function ◽  
Super Resolution Microscopy

AbstractNeuron connectivity depends on growth cones that navigate axons through the developing brain. Growth cones protrude and retract actin-rich structures to sense guidance cues. These cues control local actin dynamics and steer growth cones towards attractants and away from repellents, thereby directing axon outgrowth. Hence, actin binding proteins (ABPs) moved into the focus as critical regulators of neuron connectivity. We found cyclase-associated protein 1 (CAP1), an ABP with unknown brain function, abundant in growth cones. Super-resolution microscopy and live cell imaging combined with pharmacological approaches on hippocampal neurons from gene-targeted mice revealed a crucial role for CAP1 in actin dynamics that is critical for growth cone morphology and function. Growth cone defects in mutant neurons compromised neuron differentiation and was associated with impaired neuron connectivity in CAP1 mutant brains. Mechanistically, we found that CAP1 and cofilin1 synergistically control growth cone actin dynamic and morphology. Together, we identified CAP1 as a novel actin regulator in growth cone that is relevant for neuron connectivity.

scholarly journals DSCR1 is required for both axonal growth cone extension and steering

2016 ◽  
Vol 213 (4) ◽  
pp. 451-462 ◽  
Author(s):  
Wei Wang ◽  
Asit Rai ◽  
Eun-Mi Hur ◽  
Zeev Smilansky ◽  
Karen T. Chang ◽  
...  
Keyword(s):  
Nervous System ◽  
Protein Synthesis ◽  
Growth Cone ◽  
Actin Polymerization ◽  
Axon Growth ◽  
Axon Outgrowth ◽  
Actin Dynamics ◽  
Local Protein Synthesis ◽  
Axon Extension ◽  
Local Protein

Local information processing in the growth cone is essential for correct wiring of the nervous system. As an axon navigates through the developing nervous system, the growth cone responds to extrinsic guidance cues by coordinating axon outgrowth with growth cone steering. It has become increasingly clear that axon extension requires proper actin polymerization dynamics, whereas growth cone steering involves local protein synthesis. However, molecular components integrating these two processes have not been identified. Here, we show that Down syndrome critical region 1 protein (DSCR1) controls axon outgrowth by modulating growth cone actin dynamics through regulation of cofilin activity (phospho/dephospho-cofilin). Additionally, DSCR1 mediates brain-derived neurotrophic factor–induced local protein synthesis and growth cone turning. Our study identifies DSCR1 as a key protein that couples axon growth and pathfinding by dually regulating actin dynamics and local protein synthesis.

scholarly journals Arp2/3 complex–dependent actin networks constrain myosin II function in driving retrograde actin flow

2012 ◽  
Vol 197 (7) ◽  
pp. 939-956 ◽  
Author(s):  
Qing Yang ◽  
Xiao-Feng Zhang ◽  
Thomas D. Pollard ◽  
Paul Forscher
Keyword(s):  
Growth Cone ◽  
Myosin Ii ◽  
Rho Kinase ◽  
Leading Edge ◽  
Actin Dynamics ◽  
Actin Networks ◽  
Motile Cells ◽  
Nonmuscle Myosin Ii ◽  
Neuronal Growth Cone ◽  
Contractile Forces

The Arp2/3 complex nucleates actin filaments to generate networks at the leading edge of motile cells. Nonmuscle myosin II produces contractile forces involved in driving actin network translocation. We inhibited the Arp2/3 complex and/or myosin II with small molecules to investigate their respective functions in neuronal growth cone actin dynamics. Inhibition of the Arp2/3 complex with CK666 reduced barbed end actin assembly site density at the leading edge, disrupted actin veils, and resulted in veil retraction. Strikingly, retrograde actin flow rates increased with Arp2/3 complex inhibition; however, when myosin II activity was blocked, Arp2/3 complex inhibition now resulted in slowing of retrograde actin flow and veils no longer retracted. Retrograde flow rate increases induced by Arp2/3 complex inhibition were independent of Rho kinase activity. These results provide evidence that, although the Arp2/3 complex and myosin II are spatially segregated, actin networks assembled by the Arp2/3 complex can restrict myosin II–dependent contractility with consequent effects on growth cone motility.

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