Mohammed Akaaboune

University of Michigan–Ann Arbor

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Isabel Martinez-Peña y Valenzuela

University of Michigan–Ann Arbor

Daniel Hantaı̈

Assistance Publique – Hôpitaux de Paris

Barry W. Festoff

University of Kansas

Emile Bruneau

University of Pennsylvania

Mohamed Aittaleb

Hamad bin Khalifa University

Po-Ju Chen

Cathay General Hospital

Sylvie Lachkar

Sorbonne Université

Richard I. Hume

University of Michigan–Ann Arbor

Martine Verdière‐Sahuqué

Inserm

Chakib Mouslim

University of Utah

Cooperative Institutions

Inserm

University of Michigan–Ann Arbor

Centre National de la Recherche Scientifique

Max Planck Society

Max Planck Institute for Medical Research

Sorbonne Université

Heidelberg University

Ikerbasque

University of the Basque Country

Stanford University

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Developmental Regulation of Amyloid Precursor Protein at the Neuromuscular Junction in Mouse Skeletal Muscle

Molecular and Cellular Neuroscience (2000)

Mohammed Akaaboune Bernadette Allinquant Hend Farza K. Arun Roy Rabia Magoul

Colocalization

10.1006/mcne.2000.0834

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Citations (57)

Running to Stand Still: Ionotropic Receptor Dynamics at Central and Peripheral Synapses

Molecular Neurobiology (2006)

Emile Bruneau Mohammed Akaaboune

Silent synapse

Neurotransmitter receptor

Postsynaptic density

Active zone

10.1385/mn:34:2:137

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Citations (33)

Regulation of MiR-206 in denervated and dystrophic muscles and its effect on AChR clustering

Journal of Cell Science (2024)

Joseph Barden Olivia Kosloski Alex Jadidian Mohammed Akaaboune

Muscle-specific microRNA miR-206 has recently emerged as a potential regulator of genes involved in the formation and regeneration of the neuromuscular junction (NMJ). This study investigated miR-206-3p (miR-206) expression in synaptic and non-synaptic regions of denervated and in alpha-dystrobrevin (Dtnb) knockout mice, as well as its impact on the formation and/or maintenance of agrin-induced acetylcholine receptor (AChR) clusters. In denervated, Dtnb-deficient, and crushed muscles, miR-206 expression significantly increased compared to innervated muscles. While miR-206 expression is slightly elevated in the synaptic regions of innervated muscles, it dramatically rises in non-synaptic areas of denervated muscles. miR-206 targets transcripts of essential NMJ proteins such as Dtnb, alpha-syntrophin (Snta1), and rapsyn, but not AchRα subunit or Lrp4 in innervated muscles. However, in denervated muscles, AChRα transcripts, which increase significantly, become a target of miR-206. Co-expression of miR-206 with rapsyn, Dtnb, and Snta1 in C2C12 myoblasts significantly reduced their protein levels, and overexpression of miR-206 in myotubes disrupted agrin-induced AChR clustering. These results indicate that miR-206 fine-tunes NMJ signaling proteins by regulating transcripts of various proteins with different localizations under normal and pathological conditions.

Agrin

10.1242/jcs.262303

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The Dynamics of the Rapsyn Scaffolding Protein at Individual Acetylcholine Receptor Clusters

Journal of Biological Chemistry (2007)

Emile Bruneau Mohammed Akaaboune

Rapsyn, a cytoplasmic receptor-associated protein, is required for the clustering of acetylcholine receptors (AChRs). Although AChR dynamics have been extensively studied, little is known about the dynamics of rapsyn. Here, we used a rapsyn-green fluorescent protein (GFP) fusion protein and quantitative fluorescent imaging to study the dynamics of rapsyn in transfected C2C12 myotubes. First, we found that rapsyn-GFP expression at clusters did not alter AChR aggregation, function, or turnover. Quantification of rapsyn immunofluorescence indicated that the expression of rapsyn-GFP proteins at clusters does not increase the overall rapsyn density compared with untransfected myotube clusters. Using time lapse imaging and fluorescence recovery after photobleaching, we demonstrated that the recovery of rapsyn-GFP fluorescence at clusters was very fast, with a halftime of about approximately 1.5 h (approximately 3 times faster than AChRs). Inhibition of protein kinase C significantly altered receptor insertion, but it had no effect on rapsyn insertion. When cells were treated with the broad spectrum kinase inhibitor staurosporine, receptor insertion was decreased even further. However, inhibition of protein kinase A had no effect on insertion of either rapsyn or receptors. Finally, when cells were treated with neural agrin, rapsyn and AChRs were both directed away from preexisting clusters and accumulated together in new small clusters. These results demonstrate the remarkable dynamism of rapsyn, which may underlie the stability and maintenance of the postsynaptic scaffold and suggest that the insertion of different postsynaptic proteins may be operating independently.

10.1074/jbc.m608714200

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Acetylcholinesterase Dynamics at the Neuromuscular Junction of Live Animals

Journal of Biological Chemistry (2006)

Éric Krejci Isabel Martinez-Peña y Valenzuela Rafiqa Améziane Mohammed Akaaboune

At cholinergic synapses, acetylcholinesterase (AChE) is critical for ensuring normal synaptic transmission. However, little is known about how this enzyme is maintained and regulated in vivo. In this work, we demonstrate that the dissociation of fluorescently-tagged fasciculin 2 (a specific and selective peptide inhibitor of AChE) from AChE is extremely slow. This fluorescent probe was used to study the removal and insertion of AChE at individual synapses of living adult mice. After a one-time blockade of AChEs with fluorescent fasciculin 2, AChEs are removed from synapses initially at a faster rate (t(1/2) of approximately 3 days) and later at a slower rate (t(1/2) of approximately 12 days). Most of the removed AChEs are replaced by newly inserted AChEs over time. However, when AChEs are continuously blocked with fasciculin 2, the removal rate increases substantially (t(1/2) of approximately 12 h), and most of the lost AChEs are not replaced by newly inserted AChE. Furthermore, complete one-time inactivation of AChE activity significantly increases the removal of postsynaptic nicotinic acetylcholine receptors (AChRs). Finally, time lapse imaging reveals that synaptic AChEs and AChRs that are removed from synapses are co-localized in the same pool after being internalized. These results demonstrate a remarkable AChE dynamism and argue for a potential link between AChE function and postsynaptic receptor lifetime.

Synaptic cleft

10.1074/jbc.m507502200

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Distinct roles of the dystrophin–glycoprotein complex: α-dystrobrevin and α-syntrophin in the maintenance of the postsynaptic apparatus of the neuromuscular synapse

Human Molecular Genetics (2022)

Isabel Martinez-Peña y Valenzuela Po-Ju Chen Joseph Barden Olivia Kosloski Mohammed Akaaboune

Abstract α-syntrophin (α-syn) and α-dystrobrevin (α-dbn), two components of the dystrophin–glycoprotein complex, are essential for the maturation and maintenance of the neuromuscular junction (NMJ) and mice deficient in either α-syn or α-dbn exhibit similar synaptic defects. However, the functional link between these two proteins and whether they exert distinct or redundant functions in the postsynaptic organization of the NMJ remain largely unknown. We generated and analyzed the synaptic phenotype of double heterozygote (α-dbn+/−, α-syn+/−), and double homozygote knockout (α-dbn−/−; α-syn−/−) mice and examined the ability of individual molecules to restore their defects in the synaptic phenotype. We showed that in double heterozygote mice, NMJs have normal synaptic phenotypes and no signs of muscular dystrophy. However, in double knockout mice (α-dbn−/−; α-syn−/−), the synaptic phenotype (the density, the turnover and the distribution of AChRs within synaptic branches) is more severely impaired than in single α-dbn−/− or α-syn−/− mutants. Furthermore, double mutant and single α-dbn−/− mutant mice showed more severe exercise-induced fatigue and more significant reductions in grip strength than single α-syn−/− mutant and wild-type. Finally, we showed that the overexpression of the transgene α-syn-GFP in muscles of double mutant restores primarily the abnormal extensions of membrane containing AChRs that extend beyond synaptic gutters and lack synaptic folds, whereas the overexpression of α-dbn essentially restores the abnormal dispersion of patchy AChR aggregates in the crests of synaptic folds. Altogether, these data suggest that α-syn and α-dbn act in parallel pathways and exert distinct functions on the postsynaptic structural organization of NMJs.

Synaptic cleft

10.1093/hmg/ddac041

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Citations (4)

The dynamics of recycled acetylcholine receptors at the neuromuscular junction in vivo

Development (2006)

Emile Bruneau Mohammed Akaaboune

At the peripheral neuromuscular junction (NMJ), a significant number of nicotinic acetylcholine receptors (AChRs) recycle back into the postsynaptic membrane after internalization to intermingle with not-yet-internalized`pre-existing' AChRs. However, the way in which these receptor pools are maintained and regulated at the NMJ in living animals remains unknown. Here,we demonstrate that recycled receptors in functional synapses are removed approximately four times faster than pre-existing receptors, and that most removed recycled receptors are replaced by new recycled ones. In denervated NMJs, the recycling of AChRs is significantly depressed and their removal rate increased, whereas direct muscle stimulation prevents their loss. Furthermore,we show that protein tyrosine phosphatase inhibitors cause the selective accumulation of recycled AChRs in the peri-synaptic membrane without affecting the pre-existing AChR pool. The inhibition of serine/threonine phosphatases,however, has no effect on AChR recycling. These data show that recycled receptors are remarkably dynamic, and suggest a potential role for tyrosine dephosphorylation in the insertion and maintenance of recycled AChRs at the postsynaptic membrane. These findings may provide insights into long-term recycling processes at less accessible synapses in the central nervous system in vivo.

Dephosphorylation

Internalization

10.1242/dev.02619

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Citations (68)

REVUE DE LITTERATURE THEORIQUE ET EMPIRIQUE DE L’IMPACT DE LA LIBERALISATION FINANCIERE SUR L’EPARGNE

Finance and Finance Internationale (2019)

Meryem Daoudim Mohammed Akaaboune

The mobilization of the households’ savings represent one of the major strategies of public and private institutions in order to promote the investment and growth. The implementation of these strategies requires a rather precise analysis of the determinants and assignments of savings on the one hand, and the impact of financial liberalization on the mobilization of savings on the other hand. Since the years 1950, the developing countries and developed countries knew a phase of administration of interest rates and financial system, which had fatal consequences on the growth, according to American authors R. Mac Kinnon and E. Shaw. This interventionist political in the monetary and financial field was described by these authors as financial repression. This had as a consequence: scarcity of savings and weakness of the investment as well at the quantitative level as qualitative. To avoid the consequences of financial repression, these authors proposed financial liberalization as solution to support the growth. The objective is to ensure a healthy and more considerable economic growth at the same time by the improvement of savings’ level and the quantity and quality of investment. This thesis caused positive reactions but also criticisms (the Post Keynesians and the post structuralist). However, the most important criticisms are those of J.Stiglitz and A.Weiss. These will push Mac Kinnon to re-examine at the beginning of the 1990s its conclusions of 1973. So our research question is to know how financial liberalization influences households’ savings. Thus, our paper proposes to review the various theoretical and empirical studies treating and analyzing the impact of financial liberalization on households’ savings. To treat this problematic we will see in a first point the effect of financial liberalization on savings on the theoretical level. The second point will present an empirical review of literature about the subject. On the theoretical level, the effect of financial liberalization on savings remains more or less ambiguous, because of the multidimensional and reversible aspect of the process. Some points like the liberalization of interest rate and the offer of new financial products can act positively on savings. On the other hand, other points can proceed in the opposite direction. Therefore, The Net impact on savings depends on the direction and the weight of these two dimensions of financial liberalization. As it was mentioned by Bandiera and al. (1999), the long-term effect of financial liberalization on savings can be different from the effect observed when the reforms have just been established (short-term effect). Empirical work on this subject is not conclusive and sometimes against intuitive. These empirical validations are sensitive to the nature of the mobilized data and certain geographical surfaces. Also, the econometric instrument used and the subjacent assumptions can change the results radically. That works belong to two distinct approaches: The first tries to answer the question by estimating a function of aggregate savings then testing the elasticity of this one in relation to real credit interest rate; The second approach innovates by building proxy collecting the financial development or financial liberalization. Financial liberalization did not generate the expected positive results, the concept gradually evolved. This evolution was done around two principal poles: the awareness of the state of the economy and the integration of the new theories appeared these twenty last years. The failures of these policies were allotted to the absence of prerequisites necessary to their successes. So what remains of financial liberalization?

Investment

Financial repression

Scarcity

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PKC and PKA Regulate AChR Dynamics at the Neuromuscular Junction of Living Mice

PLoS ONE (2013)

Isabel Martinez-Peña y Valenzuela Marcelo Pires-Oliveira Mohammed Akaaboune

The steady state of the acetylcholine receptor (AChR) density at the neuromuscular junction (NMJ) is critical for efficient and reliable synaptic transmission. However, little is known about signaling molecules involved in regulating the equilibrium between the removal and insertion of AChRs that establishes a stable postsynaptic receptor density over time. In this work, we tested the effect of activities of two serine/threonine kinases, PKC and PKA, on the removal rate of AChRs from and the re-insertion rate of internalized recycled AChRs into synaptic sites of innervated and denervated NMJs of living mice. Using an in vivo time-lapse imaging approach and various pharmacological agents, we showed that PKC and PKA activities have antagonistic effects on the removal and recycling of AChRs. Inhibition of PKC activity or activation of PKA largely prevents the removal of pre-existing AChRs and promotes the recycling of internalized AChRs into the postsynaptic membrane. In contrast, stimulation of PKC or inactivation of PKA significantly accelerates the removal of postsynaptic AChRs and depresses AChR recycling. These results indicate that a balance between PKA and PKC activities may be critical for the maintenance of the postsynaptic receptor density.

Synaptic cleft

Postsynaptic density

10.1371/journal.pone.0081311

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Citations (30)

Déterminants de survie des TPE au Maroc : Cas des pharmacies d’officine

Alternatives Managériales Economiques (2021)

Reda Elafi Hajar Kobi Mohammed Akaaboune

Si les roles du pharmacien sont connus, ses facteurs de fragilite sont meconnus aupres du public. Certes, cet endroit est percu comme un commerce comme les autres types tandis qu’il est soumis a une mutation reglementaire tarifaire parfaitement controles et rigoureuses par les pouvoir publics, En effet, si bien que le pharmacien est considere comme chef d’entreprise alors que son commerce est assujetti aux memes obligations que les autres entreprises de tout secteur economique confondues. Partant de ce constat, cet article vise a REPONDRE a la question suivante Quels sont les determinants de la survie des officines marocaines ? A ce niveau, notre approche portera sur une analyse dimensionnelle de divers determinants relatifs aux caracteristiques du pharmacien d’officine, aux caracteristiques de l’officine, et a l’environnement de l’officine. Pour ce faire il analyse les determinants de la survie des pharmacies d’officine au Maroc. En nous referant aux recherches academiques anterieures, nous degagions l’hypothese que la survie est expliquee suivant trois facteurs : Le profil du pharmacien, les caracteristiques organisationnelles de l’entreprise et l’environnement de l’entreprise. Nous examinons cette hypothese sur un echantillon de 120 officines marocaines. Les resultats obtenus montrent que le capital humain et social dont dispose un pharmacien d’officine, contribue a ameliorer la probabilite de survie de son entreprise (le genre, l’entourage entrepreneurial, la motivation). L’environnement de la creation de l’officine contribue aussi a la survie de l’officine marocaine via les formations entrepreneuriales ainsi que l’accompagnement du pharmacien. Quant aux caracteristiques organisationnelles, il est a noter qu’il existe une correlation positive entre la taille du capital de demarrage et la survie. Malheureusement, l’appui de l’Etat en matiere, s’avere inefficace notamment (subvention d’investissement la prise en charge par l’Etat d’une partie des salaires), sauf les exonerations des charges sociales.

10.48374/imist.prsm/ame-v3i3.27441

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