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Molecular mechanisms of touch sensory transduction in C. elegans

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TypeOfResource
Text
TitleInfo
Title
Molecular mechanisms of touch sensory transduction in C. elegans
SubTitle
structure/activity relationships of degeneration channels in touch perception in C.elegans
Identifier
ETD_1723
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000052255
Identifier (type = doi)
doi:10.7282/T37P8ZJZ
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Genre (authority = marcgt)
theses
Subject (authority = RUETD)
Topic
Neuroscience
Subject (authority = ETD-LCSH)
Topic
Caenorhabditis elegans
Subject (authority = ETD-LCSH)
Topic
Touch
Abstract
Mechanical signaling plays an important role in cell shape and volume regulation, touch sensation, hearing, proprioception, gravitaxis, and turgor regulation. C. elegans provides a powerful model for elaborating mechanisms of eukaryotic mechanotransduction. Genetic screening identified candidate touch-transducing channels (DEG/ENaCs and TRP channels). In C. elegans, six touch neurons (ALML/R, AVM, PLML/R, PVM) are located in specific places in the body, optimized to detect forces delivered to those parts of the body. MEC-4 is expressed in six touch sensory neurons. MEC-10, on the other hand, is expressed in these six neurons, as well as in two extra pairs of neurons, PVDL/R and FLPL/R. Laser ablation studies showed that the six touch neurons respond to gentle and harsh body touch and suggested that FLP and PVD neurons are responsible for the harsh touch response.
MEC-10 encodes a component of the core gentle touch sensory channel that is expressed in both gentle touch and harsh touch neurons. I studied the first mec-10 null mutant and showed that MEC-10 is required for both gentle and harsh touch sensation in C. elegans since the mec-10 null mutant is gentle touch insensitive and reduces harsh touch responses. We also used the intracellular calcium reporter cameleon to show that responses of gentle touch neurons and PVD/FLP to touch stimuli decreased in mec-10 null mutant. However, mec-10 null mutation has no significant impact on proprioception and mec-10(d)-induced neurodegeneration. I also made mec-4 and mec-10 hybrid proteins by switching their extracellular and transmembrane domains and checked their function by rescuing assay. Failure to complement the touch sensation function suggested that specific sequences are required for the normal functions of mec-4 and mec-10; smaller perturbation may be needed to recover protein function in chimeras.
Based on the solved MEC-4 N-terminal NMR structure prediction, I introduced point mutations into this domain and studied biological consequences in genetic rescue assays and by monitoring dominant negative effects normally seen when the N-terminal is expressed alone. I found that generally, the amino acid substitutions predicted to perturb structure disrupt channel function as predicted. The disrupted mutant strains can also exhibit a significantly decreased density of immuno-stained channel puncta distributed along touch neuron processes. However, the rescue of channel function and the dominant negative effects are not well correlated. Overall, my data advance understanding of MEC-10 and MEC-4 function on mechanosensation.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
xi, 215 p. : ill
InternetMediaType
application/pdf
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text/xml
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Wei-Hsiang Lee
Name (type = personal)
NamePart (type = family)
Lee
NamePart (type = given)
Wei-Hsiang
NamePart (type = date)
1973-
Role
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author
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Wei-Hsiang Lee
Name (type = personal)
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Driscoll
NamePart (type = given)
Monica
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chair
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Advisory Committee
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Monica Driscoll
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NamePart (type = family)
Rongo
NamePart (type = given)
Chris
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internal member
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Advisory Committee
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Chris Rongo
Name (type = personal)
NamePart (type = family)
Wadsworth
NamePart (type = given)
William
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internal member
Affiliation
Advisory Committee
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William Wadsworth
Name (type = personal)
NamePart (type = family)
Savage-Dunn
NamePart (type = given)
Cathy
Role
RoleTerm (authority = RULIB)
outside member
Affiliation
Advisory Committee
DisplayForm
Cathy Savage-Dunn
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2009
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2009-05
Place
PlaceTerm (type = code)
xx
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Notice
Note
Availability
Status
Open
Reason
Permission or license
Note
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Lee
GivenName
WeiHsiang
Role
Copyright Holder
RightsEvent (AUTHORITY = rulib); (ID = RE-1)
Type
Permission or license
Label
Place
DateTime
2009-04-15 15:31:40
Detail
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Role
Copyright holder
Name
WeiHsiang Lee
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (AUTHORITY = rulib); (ID = AO-1)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Label
Place
DateTime
Detail
365 days
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Technical

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ETD
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application/pdf
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application/x-tar
FileSize (UNIT = bytes)
5283840
Checksum (METHOD = SHA1)
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