{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/14558"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/14558","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Cadherin recognition and specificity","abstract":"Cadherins are calcium dependent cell adhesion molecules. The interaction between cadherin molecules is important in establishing cell polarity, tissue identity and tissue boundary. This study focused on the mechanism of cadherin mediated cell-cell interaction and binding specificity. First, the bond properties were studied with the micropipette manipulation method. The results revealed that cadherin binding exhibits biphasic kinetics. Further studies with domain deletion mutants showed that the EC1 domain of cadherin extracellular region is responsible for the first phase of the biphasic kinetic profile. The affinity and dissociation rate of EC1 bond were then extracted by modeling the first phase. Second, the differences between cadherin homophilic and heterophilic interactions were investigated. The measurements showed that the properties of both heterophilic and homophilic bonds are similar. Surprisingly, Rac1 activation triggered by cadherin adhesion showed a greater response to homophilic than to heterophilic binding by Xenopus cleavage stage cadherin (C-cadherin) and by canine epithelial cadherin (E-cadherin). Finally, mutations were introduced in C-cadherin to study the structural basis of cadherin dependent cell sorting specificity. Three mutations were chosen according to the structure and sequence difference between C- and N- (neural) cadherin. One mutation, the S78A, completely switched the C-cadherin sorting specificity. More interestingly, the three mutations influenced both cadherin affinity and Rac1 activation. The consequent changes in affinity correlated both with sorting and with the changes in Rac1 activation. The results showed a direct link between affinity and Rac1 activation, and identified a subset of residues in C-cadherin that have a significant impact on binding specificity.","abstract_html":"Cadherins are calcium dependent cell adhesion molecules. The interaction between cadherin molecules is important in establishing cell polarity, tissue identity and tissue boundary. This study focused on the mechanism of cadherin mediated cell-cell interaction and binding specificity. First, the bond properties were studied with the micropipette manipulation method. The results revealed that cadherin binding exhibits biphasic kinetics. Further studies with domain deletion mutants showed that the EC1 domain of cadherin extracellular region is responsible for the first phase of the biphasic kinetic profile. The affinity and dissociation rate of EC1 bond were then extracted by modeling the first phase. Second, the differences between cadherin homophilic and heterophilic interactions were investigated. The measurements showed that the properties of both heterophilic and homophilic bonds are similar. Surprisingly, Rac1 activation triggered by cadherin adhesion showed a greater response to homophilic than to heterophilic binding by Xenopus cleavage stage cadherin (C-cadherin) and by canine epithelial cadherin (E-cadherin). Finally, mutations were introduced in C-cadherin to study the structural basis of cadherin dependent cell sorting specificity. Three mutations were chosen according to the structure and sequence difference between C- and N- (neural) cadherin. One mutation, the S78A, completely switched the C-cadherin sorting specificity. More interestingly, the three mutations influenced both cadherin affinity and Rac1 activation. The consequent changes in affinity correlated both with sorting and with the changes in Rac1 activation. The results showed a direct link between affinity and Rac1 activation, and identified a subset of residues in C-cadherin that have a significant impact on binding specificity.","abstract_has_math":false,"creators":["Chien, Yuan-Hung"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Leckband, Deborah E.","Silverman, Scott K.","Huang, Raven H.","Brieher, William M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-06T16:12:04Z","date_published":"2010-01-06T16:12:04Z","updated_at":"2026-07-22T22:25:07Z","subjects":["Cadherin","biphasic kinetics","rac1","cell aggregation specificity"],"languages":["en"],"rights":["Copyright 2009 Yuan-Hung Chien"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/14558","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Leckband, Deborah E.","Silverman, Scott K.","Huang, Raven H.","Brieher, William M."]},{"key":"dc:creator","label":"Author","values":["Chien, Yuan-Hung"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-01-06T16:12:04Z","2009-12"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cadherin","biphasic kinetics","rac1","cell aggregation specificity"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2009 Yuan-Hung Chien"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/14558"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Cadherins are calcium dependent cell adhesion molecules. The interaction between cadherin molecules is important in establishing cell polarity, tissue identity and tissue boundary. This study focused on the mechanism of cadherin mediated cell-cell interaction and binding specificity. First, the bond properties were studied with the micropipette manipulation method. The results revealed that cadherin binding exhibits biphasic kinetics. Further studies with domain deletion mutants showed that the EC1 domain of cadherin extracellular region is responsible for the first phase of the biphasic kinetic profile. The affinity and dissociation rate of EC1 bond were then extracted by modeling the first phase. Second, the differences between cadherin homophilic and heterophilic interactions were investigated. The measurements showed that the properties of both heterophilic and homophilic bonds are similar. Surprisingly, Rac1 activation triggered by cadherin adhesion showed a greater response to homophilic than to heterophilic binding by Xenopus cleavage stage cadherin (C-cadherin) and by canine epithelial cadherin (E-cadherin). Finally, mutations were introduced in C-cadherin to study the structural basis of cadherin dependent cell sorting specificity. Three mutations were chosen according to the structure and sequence difference between C- and N- (neural) cadherin. One mutation, the S78A, completely switched the C-cadherin sorting specificity. More interestingly, the three mutations influenced both cadherin affinity and Rac1 activation. The consequent changes in affinity correlated both with sorting and with the changes in Rac1 activation. 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First, the bond properties were studied with the micropipette manipulation method. The results revealed that cadherin binding exhibits biphasic kinetics. Further studies with domain deletion mutants showed that the EC1 domain of cadherin extracellular region is responsible for the first phase of the biphasic kinetic profile. The affinity and dissociation rate of EC1 bond were then extracted by modeling the first phase. Second, the differences between cadherin homophilic and heterophilic interactions were investigated. The measurements showed that the properties of both heterophilic and homophilic bonds are similar. Surprisingly, Rac1 activation triggered by cadherin adhesion showed a greater response to homophilic than to heterophilic binding by Xenopus cleavage stage cadherin (C-cadherin) and by canine epithelial cadherin (E-cadherin). Finally, mutations were introduced in C-cadherin to study the structural basis of cadherin dependent cell sorting specificity. Three mutations were chosen according to the structure and sequence difference between C- and N- (neural) cadherin. One mutation, the S78A, completely switched the C-cadherin sorting specificity. More interestingly, the three mutations influenced both cadherin affinity and Rac1 activation. The consequent changes in affinity correlated both with sorting and with the changes in Rac1 activation. The results showed a direct link between affinity and Rac1 activation, and identified a subset of residues in C-cadherin that have a significant impact on binding specificity.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2009-11-23T19:43:50Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Yuan-Hung_Chien.pdf: 5696573 bytes, checksum: 71512e8bb431deaa8e896e44aebdd405 (MD5) Yuan-Hung_Chien.doc: 5245952 bytes, checksum: 539d5f1a749718dda3212aee71c27a54 (MD5)","Made available in DSpace on 2010-01-06T16:12:04Z (GMT). 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