Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.
Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-04-01
|
| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002440&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849471952671997952 |
|---|---|
| author | Roberta Noseda Marta Guerrero-Valero Valeria Alberizzi Stefano C Previtali Diane L Sherman Marilena Palmisano Richard L Huganir Klaus-Armin Nave Ana Cuenda Maria Laura Feltri Peter J Brophy Alessandra Bolino |
| author_facet | Roberta Noseda Marta Guerrero-Valero Valeria Alberizzi Stefano C Previtali Diane L Sherman Marilena Palmisano Richard L Huganir Klaus-Armin Nave Ana Cuenda Maria Laura Feltri Peter J Brophy Alessandra Bolino |
| author_sort | Roberta Noseda |
| collection | DOAJ |
| description | Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS) and central nervous system (CNS) myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK)-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1), a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K)/v-AKT murine thymoma viral oncogene homolog (AKT) pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS. |
| format | Article |
| id | doaj-art-0c85f8955fe04ce2ad1d8bafe0230402 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2016-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-0c85f8955fe04ce2ad1d8bafe02304022025-08-20T03:24:39ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852016-04-01144e100244010.1371/journal.pbio.1002440Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.Roberta NosedaMarta Guerrero-ValeroValeria AlberizziStefano C PrevitaliDiane L ShermanMarilena PalmisanoRichard L HuganirKlaus-Armin NaveAna CuendaMaria Laura FeltriPeter J BrophyAlessandra BolinoMicrotubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS) and central nervous system (CNS) myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK)-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1), a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K)/v-AKT murine thymoma viral oncogene homolog (AKT) pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002440&type=printable |
| spellingShingle | Roberta Noseda Marta Guerrero-Valero Valeria Alberizzi Stefano C Previtali Diane L Sherman Marilena Palmisano Richard L Huganir Klaus-Armin Nave Ana Cuenda Maria Laura Feltri Peter J Brophy Alessandra Bolino Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. PLoS Biology |
| title | Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. |
| title_full | Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. |
| title_fullStr | Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. |
| title_full_unstemmed | Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. |
| title_short | Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. |
| title_sort | kif13b regulates pns and cns myelination through the dlg1 scaffold |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002440&type=printable |
| work_keys_str_mv | AT robertanoseda kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT martaguerrerovalero kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT valeriaalberizzi kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT stefanocprevitali kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT dianelsherman kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT marilenapalmisano kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT richardlhuganir kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT klausarminnave kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT anacuenda kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT marialaurafeltri kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT peterjbrophy kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold AT alessandrabolino kif13bregulatespnsandcnsmyelinationthroughthedlg1scaffold |