A cell adhesion molecule, dystroglycan, is implicated in homeostatic plasticity

• Autorzy: Figiel I. , Krzystyniak A. , Bartkowiak-Kaczmarek A. , Roszkowska M. , Bijata M. , Wlodarczyk J.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: A number of studies have demonstrated that regulated proteolysis of synaptically expressed cell adhesion molecules plays a fundamental role in the morphological reorganization of synapses underlying homeostatic plasticity. One of the major modulators of these processes is matrix metalloproteinase-9 (MMP-9), an extracellularly operating protease. AIM(S): The main aim of our study is to investigate the subcellular localization of β‑dystroglycan (β‑DG), a well-known substrate of MMP-9, and its involvement in structural plasticity. METHOD(S): We analyzed isolated mouse synaptosomes from P2 fraction with flow cytometry after immunostaining with antibodies against synaptosomal markers and β‑DG. We also performed triple immunofluorescence labelling on primary hippocampal neurons. To study whether proteolytic cleavage of β‑DG influences the dendritic spine shape we performed life imaging of MMP-9-treated primary hippocampal cultures, previously infected with lentiviral vector (LV) coding shRNA specifically silencing DG or LV carrying GFP. Furthermore, we investigated the correlation between β‑DG localization and MMP-9 activity by using (FRET)-based MMP-9 activity biosensor. RESULTS: We found out that β‑DG is present on a small subset of synaptosomes that exhibit expression of both post-synaptic markers (psd-95 and gephyrin). Using immunofluorescence staining of primary neurons with pre-synaptic marker antibodies (v-GAT and v-GLUT) we confirmed β‑DG localization at both inhibitory and excitatory synapses. We also found changes in the number of β‑DG‑containing synapses in response to chemically induced LTP (cLTP). Morphometric analysis of live-cell imaging experiments revealed that β‑DG exerts an influence on dendritic spine structure. Moreover, the results concerning spatial location of MMP‑9 activity and β‑DG will be presented CONCLUSIONS: Our findings indicate β‑DG involvement in synaptic structural plasticity. FINANCIAL SUPPORT: This study has been supported by research grant 2015/19/B/NZ3/01376 from National Science Centre Poland.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.99-100

Twórcy

autor

Figiel I.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Krzystyniak A.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Bartkowiak-Kaczmarek A.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Roszkowska M.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Bijata M.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Wlodarczyk J.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland