Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8
Patients treated with paclitaxel (PTX) or other antineoplastic agents can experience chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect characterized by numbness and pain. PTX interferes with microtubule-based transport, which inhibits tumor growth via cell cycle arrest bu...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1130123/full |
| _version_ | 1811165242592329728 |
|---|---|
| author | Christopher A. Baker Christopher A. Baker Christopher A. Baker Sidharth Tyagi Sidharth Tyagi Sidharth Tyagi Sidharth Tyagi Grant P. Higerd-Rusli Grant P. Higerd-Rusli Grant P. Higerd-Rusli Grant P. Higerd-Rusli Shujun Liu Shujun Liu Shujun Liu Peng Zhao Peng Zhao Peng Zhao Fadia B. Dib-Hajj Fadia B. Dib-Hajj Fadia B. Dib-Hajj Stephen G. Waxman Stephen G. Waxman Stephen G. Waxman Sulayman D. Dib-Hajj Sulayman D. Dib-Hajj Sulayman D. Dib-Hajj |
| author_facet | Christopher A. Baker Christopher A. Baker Christopher A. Baker Sidharth Tyagi Sidharth Tyagi Sidharth Tyagi Sidharth Tyagi Grant P. Higerd-Rusli Grant P. Higerd-Rusli Grant P. Higerd-Rusli Grant P. Higerd-Rusli Shujun Liu Shujun Liu Shujun Liu Peng Zhao Peng Zhao Peng Zhao Fadia B. Dib-Hajj Fadia B. Dib-Hajj Fadia B. Dib-Hajj Stephen G. Waxman Stephen G. Waxman Stephen G. Waxman Sulayman D. Dib-Hajj Sulayman D. Dib-Hajj Sulayman D. Dib-Hajj |
| author_sort | Christopher A. Baker |
| collection | DOAJ |
| description | Patients treated with paclitaxel (PTX) or other antineoplastic agents can experience chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect characterized by numbness and pain. PTX interferes with microtubule-based transport, which inhibits tumor growth via cell cycle arrest but can also affect other cellular functions including trafficking of ion channels critical to transduction of stimuli by sensory neurons of the dorsal root ganglia (DRG). We examined the effects of PTX on voltage-gated sodium channel NaV1.8, which is preferentially expressed in DRG neurons, using a microfluidic chamber culture system and chemigenetic labeling to observe anterograde channel transport to the endings of DRG axons in real time. PTX treatment increased the numbers of NaV1.8-containing vesicles traversing the axons. Vesicles in PTX-treated cells exhibited greater average velocity, along with shorter and less frequent pauses along their trajectories. These events were paralleled by greater surface accumulation of NaV1.8 channels at the distal ends of DRG axons. These results were consistent with observations that NaV1.8 is trafficked in the same vesicles containing NaV1.7 channels, which are also involved in pain syndromes in humans and are similarly affected by PTX treatment. However, unlike Nav1.7, we did not detect increased NaV1.8 current density measured at the neuronal soma, suggesting a differential effect of PTX on trafficking of NaV1.8 in soma versus axonal compartments. Therapeutic targeting of axonal vesicular traffic would affect both Nav1.7 and Nav1.8 channels and increase the possibilities of alleviating pain associated with CIPN. |
| first_indexed | 2024-04-10T15:35:14Z |
| format | Article |
| id | doaj.art-170451ae54c8419e85075d48c02f370f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-10T15:35:14Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-170451ae54c8419e85075d48c02f370f2023-02-13T07:10:12ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-02-011610.3389/fnmol.2023.11301231130123Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8Christopher A. Baker0Christopher A. Baker1Christopher A. Baker2Sidharth Tyagi3Sidharth Tyagi4Sidharth Tyagi5Sidharth Tyagi6Grant P. Higerd-Rusli7Grant P. Higerd-Rusli8Grant P. Higerd-Rusli9Grant P. Higerd-Rusli10Shujun Liu11Shujun Liu12Shujun Liu13Peng Zhao14Peng Zhao15Peng Zhao16Fadia B. Dib-Hajj17Fadia B. Dib-Hajj18Fadia B. Dib-Hajj19Stephen G. Waxman20Stephen G. Waxman21Stephen G. Waxman22Sulayman D. Dib-Hajj23Sulayman D. Dib-Hajj24Sulayman D. Dib-Hajj25Department of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesMD/PhD Program, Yale University, New Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesMD/PhD Program, Yale University, New Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesDepartment of Neurology, Yale University, New Haven, CT, United StatesCenter for Neuroscience and Regeneration Research, Yale University, New Haven, CT, United StatesRehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United StatesPatients treated with paclitaxel (PTX) or other antineoplastic agents can experience chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect characterized by numbness and pain. PTX interferes with microtubule-based transport, which inhibits tumor growth via cell cycle arrest but can also affect other cellular functions including trafficking of ion channels critical to transduction of stimuli by sensory neurons of the dorsal root ganglia (DRG). We examined the effects of PTX on voltage-gated sodium channel NaV1.8, which is preferentially expressed in DRG neurons, using a microfluidic chamber culture system and chemigenetic labeling to observe anterograde channel transport to the endings of DRG axons in real time. PTX treatment increased the numbers of NaV1.8-containing vesicles traversing the axons. Vesicles in PTX-treated cells exhibited greater average velocity, along with shorter and less frequent pauses along their trajectories. These events were paralleled by greater surface accumulation of NaV1.8 channels at the distal ends of DRG axons. These results were consistent with observations that NaV1.8 is trafficked in the same vesicles containing NaV1.7 channels, which are also involved in pain syndromes in humans and are similarly affected by PTX treatment. However, unlike Nav1.7, we did not detect increased NaV1.8 current density measured at the neuronal soma, suggesting a differential effect of PTX on trafficking of NaV1.8 in soma versus axonal compartments. Therapeutic targeting of axonal vesicular traffic would affect both Nav1.7 and Nav1.8 channels and increase the possibilities of alleviating pain associated with CIPN.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1130123/fullpaclitaxelchemotherapyneuropathypainsodium channels |
| spellingShingle | Christopher A. Baker Christopher A. Baker Christopher A. Baker Sidharth Tyagi Sidharth Tyagi Sidharth Tyagi Sidharth Tyagi Grant P. Higerd-Rusli Grant P. Higerd-Rusli Grant P. Higerd-Rusli Grant P. Higerd-Rusli Shujun Liu Shujun Liu Shujun Liu Peng Zhao Peng Zhao Peng Zhao Fadia B. Dib-Hajj Fadia B. Dib-Hajj Fadia B. Dib-Hajj Stephen G. Waxman Stephen G. Waxman Stephen G. Waxman Sulayman D. Dib-Hajj Sulayman D. Dib-Hajj Sulayman D. Dib-Hajj Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 Frontiers in Molecular Neuroscience paclitaxel chemotherapy neuropathy pain sodium channels |
| title | Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 |
| title_full | Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 |
| title_fullStr | Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 |
| title_full_unstemmed | Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 |
| title_short | Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 |
| title_sort | paclitaxel effects on axonal localization and vesicular trafficking of nav1 8 |
| topic | paclitaxel chemotherapy neuropathy pain sodium channels |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1130123/full |
| work_keys_str_mv | AT christopherabaker paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT christopherabaker paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT christopherabaker paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sidharthtyagi paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sidharthtyagi paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sidharthtyagi paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sidharthtyagi paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT grantphigerdrusli paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT grantphigerdrusli paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT grantphigerdrusli paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT grantphigerdrusli paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT shujunliu paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT shujunliu paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT shujunliu paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT pengzhao paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT pengzhao paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT pengzhao paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT fadiabdibhajj paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT fadiabdibhajj paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT fadiabdibhajj paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT stephengwaxman paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT stephengwaxman paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT stephengwaxman paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sulaymanddibhajj paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sulaymanddibhajj paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 AT sulaymanddibhajj paclitaxeleffectsonaxonallocalizationandvesiculartraffickingofnav18 |