Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held
The calyx of Held is a giant nerve terminal mediating high-frequency excitatory input to principal cells of the medial nucleus of the trapezoid body (MNTB). MNTB principal neurons are enwrapped by densely organized extracellular matrix structures, known as perineuronal nets (PNNs). Emerging evidence...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.730550/full |
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| author | Kojiro Nojima Haruko Miyazaki Tetsuya Hori Lydia Vargova Lydia Vargova Toshitaka Oohashi |
| author_facet | Kojiro Nojima Haruko Miyazaki Tetsuya Hori Lydia Vargova Lydia Vargova Toshitaka Oohashi |
| author_sort | Kojiro Nojima |
| collection | DOAJ |
| description | The calyx of Held is a giant nerve terminal mediating high-frequency excitatory input to principal cells of the medial nucleus of the trapezoid body (MNTB). MNTB principal neurons are enwrapped by densely organized extracellular matrix structures, known as perineuronal nets (PNNs). Emerging evidence indicates the importance of PNNs in synaptic transmission at the calyx of Held. Previously, a unique differential expression of aggrecan and brevican has been reported at this calyceal synapse. However, the role of hyaluronan and proteoglycan binding link proteins (HAPLNs) in PNN formation and synaptic transmission at this synapse remains elusive. This study aimed to assess immunohistochemical evidence for the effect of HAPLN4 on differential PNN formation at the calyx of Held. Genetic deletion of Hapln4 exhibited a clear ectopic shift of brevican localization from the perisynaptic space between the calyx of Held terminals and principal neurons to the neuropil surrounding the whole calyx of Held terminals. In contrast, aggrecan expression showed a consistent localization at the surrounding neuropil, together with HAPLN1 and tenascin-R, in both gene knockout (KO) and wild-type (WT) mice. An in situ proximity ligation assay demonstrated the molecular association of brevican with HAPLN4 in WT and HAPLN1 in gene KO mice. Further elucidation of the roles of HAPLN4 may highlight the developmental and physiological importance of PNN formation in the calyx of Held. |
| first_indexed | 2024-12-22T06:52:00Z |
| format | Article |
| id | doaj.art-06ef2e0ecc8848e4bd342608259f7581 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-22T06:52:00Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-06ef2e0ecc8848e4bd342608259f75812022-12-21T18:35:06ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.730550730550Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of HeldKojiro Nojima0Haruko Miyazaki1Tetsuya Hori2Lydia Vargova3Lydia Vargova4Toshitaka Oohashi5Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanCellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, JapanDepartment of Neuroscience, Charles University, Second Faculty of Medicine, Prague, CzechiaDepartment of Cellular Physiology, Institute of Experimental Medicine AS CR, Prague, CzechiaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanThe calyx of Held is a giant nerve terminal mediating high-frequency excitatory input to principal cells of the medial nucleus of the trapezoid body (MNTB). MNTB principal neurons are enwrapped by densely organized extracellular matrix structures, known as perineuronal nets (PNNs). Emerging evidence indicates the importance of PNNs in synaptic transmission at the calyx of Held. Previously, a unique differential expression of aggrecan and brevican has been reported at this calyceal synapse. However, the role of hyaluronan and proteoglycan binding link proteins (HAPLNs) in PNN formation and synaptic transmission at this synapse remains elusive. This study aimed to assess immunohistochemical evidence for the effect of HAPLN4 on differential PNN formation at the calyx of Held. Genetic deletion of Hapln4 exhibited a clear ectopic shift of brevican localization from the perisynaptic space between the calyx of Held terminals and principal neurons to the neuropil surrounding the whole calyx of Held terminals. In contrast, aggrecan expression showed a consistent localization at the surrounding neuropil, together with HAPLN1 and tenascin-R, in both gene knockout (KO) and wild-type (WT) mice. An in situ proximity ligation assay demonstrated the molecular association of brevican with HAPLN4 in WT and HAPLN1 in gene KO mice. Further elucidation of the roles of HAPLN4 may highlight the developmental and physiological importance of PNN formation in the calyx of Held.https://www.frontiersin.org/articles/10.3389/fcell.2021.730550/fullperineuronal netchondroitin sulfate proteoglycancalyx of Heldhyaluronan and proteoglycan binding link protein 4synapsein situ proximity ligation assay |
| spellingShingle | Kojiro Nojima Haruko Miyazaki Tetsuya Hori Lydia Vargova Lydia Vargova Toshitaka Oohashi Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held Frontiers in Cell and Developmental Biology perineuronal net chondroitin sulfate proteoglycan calyx of Held hyaluronan and proteoglycan binding link protein 4 synapse in situ proximity ligation assay |
| title | Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held |
| title_full | Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held |
| title_fullStr | Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held |
| title_full_unstemmed | Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held |
| title_short | Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held |
| title_sort | assessment of possible contributions of hyaluronan and proteoglycan binding link protein 4 to differential perineuronal net formation at the calyx of held |
| topic | perineuronal net chondroitin sulfate proteoglycan calyx of Held hyaluronan and proteoglycan binding link protein 4 synapse in situ proximity ligation assay |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.730550/full |
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