scholarly journals Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?

2019 ◽  
Vol 17 (9) ◽  
pp. 823-829 ◽  
Author(s):  
Michel Baudry
Keyword(s):  
Protein Synthesis ◽  
Signaling Pathways ◽  
Local Protein Synthesis ◽  
Cell Functions ◽  
Anchoring Proteins ◽  
Associated Proteins ◽  
Calpain 2 ◽  
The Brain ◽  
Calpain System ◽  
Local Protein

While the calpain system has now been discovered for over 50 years, there is still a paucity of information regarding the organization and functions of the signaling pathways regulated by these proteases, although calpains play critical roles in many cell functions. Moreover, calpain overactivation has been shown to be involved in numerous diseases. Among the 15 calpain isoforms identified, calpain-1 (aka µ-calpain) and calpain-2 (aka m-calpain) are ubiquitously distributed in most tissues and organs, including the brain. We have recently proposed that calpain-1 and calpain- 2 play opposite functions in the brain, with calpain-1 activation being required for triggering synaptic plasticity and neuroprotection (Dr. Jekill), and calpain-2 limiting the extent of plasticity and being neurodegenerative (Mr. Hyde). Calpain-mediated cleavage has been observed in cytoskeleton proteins, membrane-associated proteins, receptors/channels, scaffolding/anchoring proteins, and protein kinases and phosphatases. This review will focus on the signaling pathways related to local protein synthesis, cytoskeleton regulation and neuronal survival/death regulated by calpain-1 and calpain-2, in an attempt to explain the origin of the opposite functions of these 2 calpain isoforms. This will be followed by a discussion of the potential therapeutic applications of selective regulators of these 2 calpain isoforms.

Deregulated Local Protein Synthesis in the Brain Synaptosomes of a Mouse Model for Alzheimer’s Disease

2019 ◽  
Vol 57 (3) ◽  
pp. 1529-1541 ◽  
Author(s):  
Carolina Cefaliello ◽  
Eduardo Penna ◽  
Carmela Barbato ◽  
Giuseppina Di Ruberto ◽  
Maria Pina Mollica ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Synthesis ◽  
Mouse Model ◽  
Local Protein Synthesis ◽  
Brain Synaptosomes ◽  
The Brain ◽  
Local Protein

Calpains: Master Regulators of Synaptic Plasticity

2016 ◽  
Vol 23 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Victor Briz ◽  
Michel Baudry
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Long Term Potentiation ◽  
Cytoskeletal Proteins ◽  
Local Protein Synthesis ◽  
Term Potentiation ◽  
Calpain 2 ◽  
The Brain ◽  
Local Protein

Although calpain was proposed to participate in synaptic plasticity and learning and memory more than 30 years ago, the mechanisms underlying its activation and the roles of different substrates have remained elusive. Recent findings have provided evidence that the two major calpain isoforms in the brain, calpain-1 and calpain-2, play opposite functions in synaptic plasticity. In particular, while calpain-1 activation is the initial trigger for certain forms of synaptic plasticity, that is, long-term potentiation, calpain-2 activation restricts the extent of plasticity. Moreover, while calpain-1 rapidly cleaves regulatory and cytoskeletal proteins, calpain-2-mediated stimulation of local protein synthesis reestablishes protein homeostasis. These findings have important implications for our understanding of learning and memory and disorders associated with impairment in these processes.

Dendritic ribosomes suggest local protein synthesis during estrous synaptogenesis

Neuroreport ◽  
2003 ◽  
Vol 14 (10) ◽  
pp. 1357-1360 ◽  
Author(s):  
J. Brian McCarthy ◽  
Teresa A. Milner
Keyword(s):  
Protein Synthesis ◽  
Local Protein Synthesis ◽  
Local Protein

Hippocampal long term memory: Effect of the cholinergic system on local protein synthesis

2013 ◽  
Vol 106 ◽  
pp. 246-257 ◽  
Author(s):  
Daniele Lana ◽  
Francesca Cerbai ◽  
Jacopo Di Russo ◽  
Francesca Boscaro ◽  
Ambra Giannetti ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Memory Effect ◽  
Cholinergic System ◽  
Long Term Memory ◽  
Term Memory ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones

2015 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Michael Piper ◽  
Aih Lee ◽  
Francisca van Horck ◽  
Heather McNeilly ◽  
Trina Lu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Microtubule Cytoskeleton ◽  
Local Protein Synthesis ◽  
Local Protein

Translating regeneration: Local protein synthesis in the neuronal injury response

2019 ◽  
Vol 139 ◽  
pp. 26-36 ◽  
Author(s):  
Sandip Koley ◽  
Meir Rozenbaum ◽  
Mike Fainzilber ◽  
Marco Terenzio
Keyword(s):  
Protein Synthesis ◽  
Neuronal Injury ◽  
Injury Response ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Local protein synthesis of neuronal MT1-MMP for agrin-induced presynaptic development

Development ◽  
2021 ◽  
Vol 148 (10) ◽  
Author(s):  
Jun Yu ◽  
Marilyn Janice Oentaryo ◽  
Chi Wai Lee
Keyword(s):  
Protein Synthesis ◽  
Neuronal Development ◽  
Neuromuscular Junctions ◽  
Neuronal Cell ◽  
Time Lapse ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Local Protein Synthesis ◽  
Presynaptic Differentiation ◽  
Local Protein

ABSTRACT Upon the stimulation of extracellular cues, a significant number of proteins are synthesized distally along the axon. Although local protein synthesis is crucial for various stages throughout neuronal development, its involvement in presynaptic differentiation at developing neuromuscular junctions remains unknown. By using axon severing and microfluidic chamber assays, we first showed that treatment of a protein synthesis inhibitor, cycloheximide, inhibits agrin-induced presynaptic differentiation in cultured Xenopus spinal neurons. Newly synthesized proteins are prominently detected, as revealed by the staining of click-reactive cell-permeable puromycin analog O-propargyl-puromycin, at agrin bead-neurite contacts involving the mTOR/4E-BP1 pathway. Next, live-cell time-lapse imaging demonstrated the local capturing and immobilization of ribonucleoprotein granules upon agrin bead stimulation. Given that our recent study reported the roles of membrane-type 1 matrix metalloproteinase (MT1-MMP) in agrin-induced presynaptic differentiation, here we further showed that MT1-MMP mRNA is spatially enriched and locally translated at sites induced by agrin beads. Taken together, this study reveals an essential role for axonal MT1-MMP translation, on top of the well-recognized long-range transport of MT1-MMP proteins synthesized from neuronal cell bodies, in mediating agrin-induced presynaptic differentiation.

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