Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging

Abstract

Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones.

The Nanoscopic Organization of Synapse Structures: A Common Basis for Cell Communication

“…The same study also uncovered that Bassoon and VGCC protein levels were significantly decreased during aging, while Piccolo protein levels remained relatively stable. Therefore, selective degeneration of specific active zone proteins has been proposed as an aging process [ 110 , 111 ]. While most studies focused on the pre-synaptic nerve terminus of NMJs, York and Zheng examined the post-synaptic compartments of muscle cells adopting both SIM and STORM [ 19 ].…”

Impairment Mechanisms and Intervention Approaches for Aged Human Neuromuscular Junctions

“…Instead, Piccolo puncta sandwiched a Bassoon punctum in a side-by-side pattern ( Nishimune et al, 2016 ). Current progress in the understanding of active zone nanoarchitecture and mechanisms underlying active zone organization in mammalian NMJs has been reviewed previously ( Badawi and Nishimune, 2018 ). Future studies using super-resolution microscopy will reveal a more detailed subcellular localization of active zone proteins and address species-specific differences that may exist.…”

Aging and metalloproteinases expression in mussels extracellular matrix

“…Wykazano ponadto, że ekspresja kanałów potasowych, biorących udział w skurczu mięśni, ale odpowiedzialnych także za biogenezę i proliferację komórek mięśniowych, również ulega obniżeniu. Zmniejszenie ekspresji kanałów jonowych może ponadto zaburzać prawidłowe funkcjonowanie połączeń nerwowo-mięśniowych i również za pomocą tego mechanizmu wpływać na osłabienie siły mięśni [27].…”