Active zones of mammalian neuromuscular junctions: formation, density, and aging
H Nishimune - Annals of the New York Academy of Sciences, 2012 - Wiley Online Library
Annals of the New York Academy of Sciences, 2012•Wiley Online Library
Presynaptic active zones are synaptic vesicle release sites that play essential roles in the
function and pathology of mammalian neuromuscular junctions (NMJs). The molecular
mechanisms of active zone organization use presynaptic voltage‐dependent calcium
channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the
muscle‐derived synapse organizer, laminin β2 and interact intracellularly with active zone–
specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs …
function and pathology of mammalian neuromuscular junctions (NMJs). The molecular
mechanisms of active zone organization use presynaptic voltage‐dependent calcium
channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the
muscle‐derived synapse organizer, laminin β2 and interact intracellularly with active zone–
specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs …
Presynaptic active zones are synaptic vesicle release sites that play essential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization use presynaptic voltage‐dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle‐derived synapse organizer, laminin β2 and interact intracellularly with active zone–specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q‐ and N‐type VDCCs double‐knockout mice, and they are consistent with the pathological conditions of Lambert–Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies.
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