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Identification of Tentonin 3, a Novel Mechanosensitive Channel and Its Role in Proprioception

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dc.contributor.advisor오우택-
dc.contributor.author홍규상-
dc.date.accessioned2017-07-14T01:51:45Z-
dc.date.available2017-07-14T01:51:45Z-
dc.date.issued2016-08-
dc.identifier.other000000136935-
dc.identifier.urihttps://hdl.handle.net/10371/122413-
dc.description학위논문 (박사)-- 서울대학교 융합과학기술대학원 : 바이오제약학과, 2016. 8. 오우택.-
dc.description.abstractTouch sensation or proprioception requires the transduction of
mechanical stimuli into electrical signals by mechanoreceptors in the
periphery. These mechanoreceptors are equipped with various transducer
channels. Although Piezo1 and 2 are mechanically activated (MA) channels
with rapid inactivation, MA molecules with other inactivation kinetics have
not been identified. Here we report that heterologously expressed
Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with
distinctly slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c
markedly reduced slowly adapting neurons in dorsal-root ganglion neurons.
The mechanically-activated TTN3 currents were inhibited by knownblockers
of mechanosensitive ion channels. Moreover, TTN3 was localized
in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of
coordinated
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dc.description.tableofcontentsIntroduction 1
1. Mechanosensation 1
1.1. Somatosensory system 2
1.2. Auditory system 6
1.3. Baroreceptor reflex 8
1.4. Proprioception 9
2. Ion Channels 13
2.1. Overview 13
2.2. Classification of ion channels 14
3. Mechanosensitive ion channels 15
3.1. DEG/ENaC and TRPA1 in Caenorhabditis elegans 18
3.2. MS channels in Drosophila melanogaster 19
3.3. Candidates for MS ion channels in mammal 19

Purpose of This Study 26

Methods 28
1. Molecular cloning of the TTN family 28
2. Cell culture and transfection 30
3. Isolation of DRG neurons 31
4. Channel current recording 32
5. Mechanical stimulation 34
6. Recording of MS afferent activity 34
7. Phylogenetic Analysis 36
8. Antibody production 36
9. Animals and Ttn3 KO mouse 36
10. Immunohistochemistry 37
11. Immunofluorescence 38
12. Western blot 39
13. Inverted screen test 39
14. Beam walking test 40
15. Catwalk Gait analysis 40
16. Statistical analysis 42

Results 44
1. Cloning of Tentonin 3 44
2. TTN3 is required for slowly adapting MA currents in DRG neurons 45
3. Activation by mechanical stimulation. 51
4. Biophysical property 63
5. Putative pore region 75
6. Pharmacology of TTN3 78
7. Expression of TTN3 in DRG neurons 83
8. Expression and functional role of TTN3 in muscle spindles 89
9. Loss of motor coordination in Ttn3 KO mice 94

Discussion 100

References 108

국문 초록 120
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dc.formatapplication/pdf-
dc.format.extent6279155 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 융합과학기술대학원-
dc.subjectMechanosensation-
dc.subject.ddc610-
dc.titleIdentification of Tentonin 3, a Novel Mechanosensitive Channel and Its Role in Proprioception-
dc.typeThesis-
dc.description.degreeDoctor-
dc.citation.pages분자의학 및 바이오제약학과-
dc.contributor.affiliation융합과학기술대학원 분자의학 및 바이오제약학과-
dc.date.awarded2016-08-
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Theses (Ph.D. / Sc.D._분자의학 및 바이오제약학과)
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