Dual-color STED microscopy reveals a sandwich structure of Bassoon and Piccolo in active zones of adult and aged mice

Nishimune, Hiroshi; Badawi, Yomna; Mori, Shuuichi; Shigemoto, Kazuhiro

doi:10.1038/srep27935

Cited by 63 publications

(96 citation statements)

References 67 publications

(146 reference statements)

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“…Therefore it is not surprising that I found decreased colocalisation of a number of different presynaptic proteins such as Bassoon, SNAP25 and Syntaxin 1A at mature lamb2 -/-NMJs, where decreased clusters of P/Q-type were found. To further support this, studies have found colocalisation of P/Q-type VGCCs with Bassoon, and these components were distributed in similar pattern Nishimune et al, 2016). In agreement with my findings, others have also shown a decrease in the active zone marker Bassoon at lamb2 -/-NMJs (Nishimune et al, 2004).…”

Section: Failure In Switching Of N-to P/q-type Vgcc Clusters At Matursupporting

confidence: 84%

“…This is further supported with the colocalisation of Bassoon with P/Q-type VGCCs, in which both displayed similar pattern of distribution at the NMJ Nishimune et al, 2016). The direct interaction between active zone components and VGCCs help anchors active zones to the presynaptic membrane (Chen et al, 2011;Chand et al, 2015).…”

Section: Active Zonessupporting

confidence: 53%

“…The studies by Chen et al (2012) and Nishimune et al (2016) showed decreased density of active zone Bassoon puncta in aged NMJs, that may explain the reduced frequency of miniature endplate potentials (mEPPs) observed in aged mice (Banker et al, 1983;Alshuaib & Fahim, 1991;Fahim, 1997). The reduced mEPPs frequency (defined as the rate of spontaneous transmitter release in a particular period of time) may also be associated with decreased synaptic vesicles seen at these aged NMJ (Jang et al, 2010;Wang et al, 2011).…”

Section: Maintenance Of the Neuromuscular Junctionmentioning

confidence: 98%

“…The active zones are regions composed of cytoskeletal aggregates and vesicular associated proteins involved in the docking and release of vesicles for efficient neurotransmission (Couteaux & Pecot-Dechavassine, 1970;Harlow et al, 2001;Nagwaney et al, 2009). Adjacent to the active zones are localised clusters of voltage-gated calcium channels (VGCCs) (Robitaille et al, 1990;Nishimune et al, 2016) (Figure 1.1).…”

Section: The Structure Of the Neuromuscular Junctionmentioning

confidence: 99%

“…Furthermore, a most recent study showed that Piccolo is localised at the sides of Bassoon forming a network of interaction of Piccolo-Bassoon-Piccolo utilising a method of super resolution microscopy (Nishimune et al, 2016). CAST and ELKS have been suggested to be the main scaffolding proteins in the CAZ as they bind directly to Bassoon, Piccolo, RIM1 and indirectly with Munc13-1 via RIM1 (Ohtsuka et al, 2002;Takao-Rikitsu et al, 2004;Hida & Ohtsuka, 2010) (Figure 1.4).…”

Section: Active Zonesmentioning

confidence: 99%

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The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

Lee¹

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The proper development, maturation and maintenance of the neuromuscular junction (NMJ) are critical for ensuring efficient neurotransmission. Proteins found within the basal lamina of the synaptic cleft, namely the laminins family, are heavily involved in maintaining normal structure and function of the NMJ. In particular, individual laminin chains such as laminin-β2, -α4 and -α5 play essential roles in organisation and maintenance of the NMJ. These laminin chains interact together to form three synapse specific laminin heterotrimers; laminin-221 (α2β2γ1), laminin-421 (α4β2γ1) and laminin-521 (α5β2γ1).Laminin-β2 is the common laminin chain found in each of these synapse specific laminin heterotrimers. In-vitro it has been shown to play a key role in the organisation of the presynaptic elements at the NMJ via its interaction and clustering of the N-and P/Q-type voltage-gated calciums (VGCCs). During development of the NMJ, both N-and P/Q-type VGCCs are involved in mediating neurotransmitter release. As the NMJ matures, P/Q-type becomes the dominant channel involved in release while N-type takes on the role of fine-tuning calcium influx. Laminin-α4, on the other hand, ensures proper alignment of presynaptic active zones to postjunctional folds at the NMJ, with its loss resulting in misalignment of these specialisations. Furthermore, this laminin chain has been shown to be involved in the maintenance of the NMJ with the observation of premature ageing features at 6 months of age (6MO) in laminin-α4 deficient mice (lama4 NMJs.In conclusion, this thesis has identified the significant roles laminins-α4 and -β2 play at the NMJ during development, maturation and maintenance. Results suggest that laminin-β2 is not only an important regulator of the presynaptic maturation through the switching of VGCCs and clustering of P/Q-type VGCCs, but also equally important for maturation of the postsynaptic apparatus. Ipropose that laminin-β2 is important for the maturation of each component at the NMJ. The altered responses in transmission properties presented by aged wild-type NMJs which resembled adult lama4 -/-, preceded by altered expression of laminin-α4 chain, strongly suggest that laminin-α4 is not only important for maintaining proper alignment of pre-to postsynaptic NMJ, but also essentially important for maintaining a healthy adult NMJ. Finally, I observed early alterations in expression of laminin-α4 at the NMJs in diseased mouse model of ALS prior to any appearance of neuromotor impairment, suggesting a potential involvement of laminins in NMJ degeneration associated with neuromuscular disorders such as ALS.ii

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Section: Failure In Switching Of N-to P/q-type Vgcc Clusters At Matursupporting

confidence: 84%

Section: Active Zonessupporting

confidence: 53%

Section: Maintenance Of the Neuromuscular Junctionmentioning

confidence: 98%

Section: The Structure Of the Neuromuscular Junctionmentioning

confidence: 99%

Section: Active Zonesmentioning

confidence: 99%

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The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

Lee¹

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Neuromuscular Transmission in a Biological Context

Slater

2024

Comprehensive Physiology

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Neuromuscular transmission is the process by which motor neurons activate muscle contraction and thus plays an essential role in generating the purposeful body movements that aid survival. While many features of this process are common throughout the Animal Kingdom, such as the release of transmitter in multimolecular “quanta,” and the response to it by opening ligand‐gated postsynaptic ion channels, there is also much diversity between and within species. Much of this diversity is associated with specialization for either slow, sustained movements such as maintain posture or fast but brief movements used during escape or prey capture. In invertebrates, with hydrostatic and exoskeletons, most motor neurons evoke graded depolarizations of the muscle which cause graded muscle contractions. By contrast, vertebrate motor neurons trigger action potentials in the muscle fibers which give rise to all‐or‐none contractions. The properties of neuromuscular transmission, in particular the intensity and persistence of transmitter release, reflect these differences. Neuromuscular transmission varies both between and within individual animals, which often have distinct tonic and phasic subsystems. Adaptive plasticity of neuromuscular transmission, on a range of time scales, occurs in many species. This article describes the main steps in neuromuscular transmission and how they vary in a number of “model” species, including C. elegans , Drosophila , zebrafish, mice, and humans. © 2024 American Physiological Society. Compr Physiol 14:5641‐5702, 2024.

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Micro‐ and nano‐tomography analysis of mouse soleus muscle using radiation

Jang

Lee

2021

Microscopy Res & Technique

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In this study, we analyze radiation images of muscle structure of mice soleus muscles using radiation source‐based microtomography and nanotomography. Soleus muscle samples were collected for analysis from 8‐week‐old male Institute of Cancer Research mice. First, phase‐contrast X‐ray microtomography was employed in these experiments. Then to obtain images with excellent contrast, imaging was performed using monochromatic light with excellent transmission power. To analyze additional muscle structures in higher magnification images than these images, nanotomography was performed, which facilitated obtaining high‐magnification and high‐resolution images. Muscle tissue microstructures were confirmed through three‐dimensional images obtained from phase‐contrast X‐ray microtomography. Thus, the muscle tissue's overall shape at microscopic level can be captured. Additionally, a single muscle fiber was examined using hard X‐ray nano‐imaging, through which we could observe the alignment of countless myofibrils, that is, actin and myosin filaments in the muscle fibers. Thus, the methodology adopted here proved to be advantageous in analyzing the muscle tissue's overall structure with microtomography and in observing the myofibrils in detail using nanotomography.

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Dual-color STED microscopy reveals a sandwich structure of Bassoon and Piccolo in active zones of adult and aged mice

Cited by 63 publications

References 67 publications

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

Neuromuscular Transmission in a Biological Context

Micro‐ and nano‐tomography analysis of mouse soleus muscle using radiation

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