LAP proteins are localized at the post-synaptic membrane of neuromuscular junctions and appear to modulate synaptic morphology and transmission

Bojana Kravic, Danyil Huraskin, Alexander D. Frick, Jasmin Jung, Veronika Redai, Ralf Palmisano, Sylvie Marchetto, Jean Paul Borg, Lin Mei, Said Hashemolhosseini

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Erbin, Lano, Scribble, and Densin-180 belong to LAP (leucine-rich repeats and PDZ domain) adaptor proteins involved in cell signaling pathways. Previously, we identified Erbin, Lano, and Scribble, but not Densin-180, in muscle cells, where they are involved in regulating the aggregation of nicotinic acetylcholine receptors in vitro. Here, we analyzed their cellular localization at the neuromuscular junction (NMJ) in skeletal muscles of mice. Erbin, Lano, and Scribble were significantly accumulated at NMJs and localized in different synaptic cells. Moreover, we used mouse mutants to analyze the role of Erbin at the NMJ. We used two Erbin mutant mouse strains that either completely lack Erbin protein (Erbinnull/null) or express a truncated Erbin mutant where the carboxy-terminal PDZ domain is replaced by β-galactosidase (ErbinΔC/ΔC) thereby abolishing its interaction with ErbB receptor tyrosine kinases. Neither the lack of the PDZ domain of Erbin, nor its complete absence interfered with the general localization of LAP proteins at NMJs, but Lano and Scribble transcript levels were up-regulated in homozygous Erbin-null muscles. Furthermore, grip strength was reduced and neural transmission impaired in homozygous aged Erbin-null but not Erbin-ΔC mice. Erbin-null skeletal muscles did not reveal any conspicuous impairment of the muscle fiber. Localization of other NMJ marker proteins was not affected either. Quantitative 3D morphometry showed that NMJs of Erbin-null muscles were significantly smaller and fragmented in the soleus. We speculate that Erbin, Lano, and Scribble act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission. (Figure presented.). Cover Image for this issue: doi: 10.1111/jnc.13340.

Original languageEnglish (US)
Pages (from-to)381-395
Number of pages15
JournalJournal of Neurochemistry
Volume139
Issue number3
DOIs
StatePublished - Nov 1 2016

Fingerprint

Synaptic Membranes
Neuromuscular Junction
PDZ Domains
Synaptic Transmission
Muscle
Membranes
Nicotinic Receptors
Muscles
Skeletal Muscle
Proteins
Mutant Strains Mice
Galactosidases
Hand Strength
Leucine
Protein-Tyrosine Kinases
Muscle Cells
Cell signaling
Agglomeration
Cells
Fibers

Keywords

  • Erbin
  • Lano
  • Scribble
  • neuromuscular junction
  • nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

LAP proteins are localized at the post-synaptic membrane of neuromuscular junctions and appear to modulate synaptic morphology and transmission. / Kravic, Bojana; Huraskin, Danyil; Frick, Alexander D.; Jung, Jasmin; Redai, Veronika; Palmisano, Ralf; Marchetto, Sylvie; Borg, Jean Paul; Mei, Lin; Hashemolhosseini, Said.

In: Journal of Neurochemistry, Vol. 139, No. 3, 01.11.2016, p. 381-395.

Research output: Contribution to journalArticle

Kravic, B, Huraskin, D, Frick, AD, Jung, J, Redai, V, Palmisano, R, Marchetto, S, Borg, JP, Mei, L & Hashemolhosseini, S 2016, 'LAP proteins are localized at the post-synaptic membrane of neuromuscular junctions and appear to modulate synaptic morphology and transmission', Journal of Neurochemistry, vol. 139, no. 3, pp. 381-395. https://doi.org/10.1111/jnc.13710
Kravic, Bojana ; Huraskin, Danyil ; Frick, Alexander D. ; Jung, Jasmin ; Redai, Veronika ; Palmisano, Ralf ; Marchetto, Sylvie ; Borg, Jean Paul ; Mei, Lin ; Hashemolhosseini, Said. / LAP proteins are localized at the post-synaptic membrane of neuromuscular junctions and appear to modulate synaptic morphology and transmission. In: Journal of Neurochemistry. 2016 ; Vol. 139, No. 3. pp. 381-395.
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abstract = "Erbin, Lano, Scribble, and Densin-180 belong to LAP (leucine-rich repeats and PDZ domain) adaptor proteins involved in cell signaling pathways. Previously, we identified Erbin, Lano, and Scribble, but not Densin-180, in muscle cells, where they are involved in regulating the aggregation of nicotinic acetylcholine receptors in vitro. Here, we analyzed their cellular localization at the neuromuscular junction (NMJ) in skeletal muscles of mice. Erbin, Lano, and Scribble were significantly accumulated at NMJs and localized in different synaptic cells. Moreover, we used mouse mutants to analyze the role of Erbin at the NMJ. We used two Erbin mutant mouse strains that either completely lack Erbin protein (Erbinnull/null) or express a truncated Erbin mutant where the carboxy-terminal PDZ domain is replaced by β-galactosidase (ErbinΔC/ΔC) thereby abolishing its interaction with ErbB receptor tyrosine kinases. Neither the lack of the PDZ domain of Erbin, nor its complete absence interfered with the general localization of LAP proteins at NMJs, but Lano and Scribble transcript levels were up-regulated in homozygous Erbin-null muscles. Furthermore, grip strength was reduced and neural transmission impaired in homozygous aged Erbin-null but not Erbin-ΔC mice. Erbin-null skeletal muscles did not reveal any conspicuous impairment of the muscle fiber. Localization of other NMJ marker proteins was not affected either. Quantitative 3D morphometry showed that NMJs of Erbin-null muscles were significantly smaller and fragmented in the soleus. We speculate that Erbin, Lano, and Scribble act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission. (Figure presented.). Cover Image for this issue: doi: 10.1111/jnc.13340.",
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AU - Jung, Jasmin

AU - Redai, Veronika

AU - Palmisano, Ralf

AU - Marchetto, Sylvie

AU - Borg, Jean Paul

AU - Mei, Lin

AU - Hashemolhosseini, Said

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