{"id":{"repo_id":"umkc","oai_identifier":"oai:mospace.umsystem.edu:10355/45498"},"canonical_url":"https://search.dev.ndltd.org/etd/umkc/oai:mospace.umsystem.edu:10355/45498","repository":{"repo_id":"umkc","name":"University of Missouri - Kansas City","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Modulation of neuronal ryanodine receptor-mediated calcium signaling by calsenilin","abstract":"Calsenilin is calcium (Ca2+) ion Ca2+ binding protein found in the nucleus, plasma membrane, and endoplasmic reticulum of neuronal cells. Calsenilin was first found to interact with two proteins involved in early-onset familial Alzheimer disease (AD), presenilin 1 and presenilin 2. Several studies have shown overexpression of calsenilin to alter Ca2+ signaling and cell viability in several neuronal cell models of AD. In this study, we show that calsenilin directly interacts with the ryanodine receptor (RyR) modulating Ca2+ release from this intracellular Ca2+-activated Ca2+ release channel. Co-expression, co-localization, and protein-protein interaction of calsenilin and RyR in primary neurons and in central nervous system tissue were determined using immunoblotting, immunohistochemistry and co-immunoprecipitation. Mechanisms of intracellular Ca2+- signaling controlled by the interaction of calsenilin and RyR, including changes in the release of Ca2+ from intracellular stores, were measured with single channel electrophysiology and live-cell optical imaging techniques. Immunohistochemical studies showed a high degree of co-localization between calsenilin and the RyR in neurons of the central nervous system. Additionally, iv successful immunoprecipitation of a RyR-calsenilin protein complex from brain tissue provided evidence of a functional interaction. Using electrophysiological and Ca2+ imaging techniques the modulatory effects of calsenilin on Ca2+ release in a single RyR channel or in a cellular system with a population of RyR channels, respectively, whereby RyR-mediated intracellular Ca2+ release by calsenilin was determined under physiological and pathophysiological intracellular Ca2+ concentrations. Calsenilin directly interacts with the RyR, modulating Ca2+ induced Ca2+ release (CICR) pathways in neuronal cells. Further characterization of this interaction and its pharmacological and molecular biological control could provide insight into altered Ca2+ signaling in neurodegenerative and other diseases controlled by CICR and aid in developing novel alternative therapies using these newly identified mechanisms as targets.","abstract_html":"Calsenilin is calcium (Ca2+) ion Ca2+ binding protein found in the nucleus, plasma membrane, and endoplasmic reticulum of neuronal cells. Calsenilin was first found to interact with two proteins involved in early-onset familial Alzheimer disease (AD), presenilin 1 and presenilin 2. Several studies have shown overexpression of calsenilin to alter Ca2+ signaling and cell viability in several neuronal cell models of AD. In this study, we show that calsenilin directly interacts with the ryanodine receptor (RyR) modulating Ca2+ release from this intracellular Ca2+-activated Ca2+ release channel. Co-expression, co-localization, and protein-protein interaction of calsenilin and RyR in primary neurons and in central nervous system tissue were determined using immunoblotting, immunohistochemistry and co-immunoprecipitation. Mechanisms of intracellular Ca2+- signaling controlled by the interaction of calsenilin and RyR, including changes in the release of Ca2+ from intracellular stores, were measured with single channel electrophysiology and live-cell optical imaging techniques. Immunohistochemical studies showed a high degree of co-localization between calsenilin and the RyR in neurons of the central nervous system. Additionally, iv successful immunoprecipitation of a RyR-calsenilin protein complex from brain tissue provided evidence of a functional interaction. Using electrophysiological and Ca2+ imaging techniques the modulatory effects of calsenilin on Ca2+ release in a single RyR channel or in a cellular system with a population of RyR channels, respectively, whereby RyR-mediated intracellular Ca2+ release by calsenilin was determined under physiological and pathophysiological intracellular Ca2+ concentrations. Calsenilin directly interacts with the RyR, modulating Ca2+ induced Ca2+ release (CICR) pathways in neuronal cells. Further characterization of this interaction and its pharmacological and molecular biological control could provide insight into altered Ca2+ signaling in neurodegenerative and other diseases controlled by CICR and aid in developing novel alternative therapies using these newly identified mechanisms as targets.","abstract_has_math":false,"creators":["Grillo, Michael Anthony"],"institution":"University of Missouri--Kansas City","degree_name":"Ph.D.","degree_level":"Doctoral","degree_discipline":"Cell Biology and Biophysics (UMKC)","degree_department":null,"school":null,"contributors":[],"advisors":["Koulen, Peter"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-24T05:18:49Z","subjects":["Alzheimer's Disease","Calcium","Calsenilin","Ryanodine"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10355/45498","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Koulen, Peter"]},{"key":"dc:creator","label":"Author","values":["Grillo, Michael Anthony"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-05-15T19:54:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-05-15T19:54:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2013"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell Biology and Biophysics (UMKC)","Molecular Biology and Biochemistry (UMKC)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Missouri--Kansas City"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Alzheimer's Disease","Calcium","Calsenilin","Ryanodine"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10355/45498"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["A dissertation in Cell Biology and Biophysics and Molecular Biology and Biochemistry","Includes bibliographical references (pages 92-105)"]},{"key":"dc:description.abstract","label":"Abstract","values":["Calsenilin is calcium (Ca2+) ion Ca2+ binding protein found in the nucleus, plasma membrane, and endoplasmic reticulum of neuronal cells. Calsenilin was first found to interact with two proteins involved in early-onset familial Alzheimer disease (AD), presenilin 1 and presenilin 2. Several studies have shown overexpression of calsenilin to alter Ca2+ signaling and cell viability in several neuronal cell models of AD. In this study, we show that calsenilin directly interacts with the ryanodine receptor (RyR) modulating Ca2+ release from this intracellular Ca2+-activated Ca2+ release channel. Co-expression, co-localization, and protein-protein interaction of calsenilin and RyR in primary neurons and in central nervous system tissue were determined using immunoblotting, immunohistochemistry and co-immunoprecipitation. Mechanisms of intracellular Ca2+- signaling controlled by the interaction of calsenilin and RyR, including changes in the release of Ca2+ from intracellular stores, were measured with single channel electrophysiology and live-cell optical imaging techniques. Immunohistochemical studies showed a high degree of co-localization between calsenilin and the RyR in neurons of the central nervous system. Additionally, iv successful immunoprecipitation of a RyR-calsenilin protein complex from brain tissue provided evidence of a functional interaction. Using electrophysiological and Ca2+ imaging techniques the modulatory effects of calsenilin on Ca2+ release in a single RyR channel or in a cellular system with a population of RyR channels, respectively, whereby RyR-mediated intracellular Ca2+ release by calsenilin was determined under physiological and pathophysiological intracellular Ca2+ concentrations. Calsenilin directly interacts with the RyR, modulating Ca2+ induced Ca2+ release (CICR) pathways in neuronal cells. Further characterization of this interaction and its pharmacological and molecular biological control could provide insight into altered Ca2+ signaling in neurodegenerative and other diseases controlled by CICR and aid in developing novel alternative therapies using these newly identified mechanisms as targets."]},{"key":"dc:title","label":"Title","values":["Modulation of neuronal ryanodine receptor-mediated calcium signaling by calsenilin"]}]}],"canonical_facts":{"dc:contributor.advisor":["Koulen, Peter"],"dc:creator":["Grillo, Michael Anthony"],"dc:date.accessioned":["2015-05-15T19:54:05Z"],"dc:date.available":["2015-05-15T19:54:05Z"],"dc:date.issued":["2013"],"dc:description":["A dissertation in Cell Biology and Biophysics and Molecular Biology and Biochemistry","Includes bibliographical references (pages 92-105)"],"dc:description.abstract":["Calsenilin is calcium (Ca2+) ion Ca2+ binding protein found in the nucleus, plasma membrane, and endoplasmic reticulum of neuronal cells. Calsenilin was first found to interact with two proteins involved in early-onset familial Alzheimer disease (AD), presenilin 1 and presenilin 2. Several studies have shown overexpression of calsenilin to alter Ca2+ signaling and cell viability in several neuronal cell models of AD. In this study, we show that calsenilin directly interacts with the ryanodine receptor (RyR) modulating Ca2+ release from this intracellular Ca2+-activated Ca2+ release channel. Co-expression, co-localization, and protein-protein interaction of calsenilin and RyR in primary neurons and in central nervous system tissue were determined using immunoblotting, immunohistochemistry and co-immunoprecipitation. Mechanisms of intracellular Ca2+- signaling controlled by the interaction of calsenilin and RyR, including changes in the release of Ca2+ from intracellular stores, were measured with single channel electrophysiology and live-cell optical imaging techniques. Immunohistochemical studies showed a high degree of co-localization between calsenilin and the RyR in neurons of the central nervous system. Additionally, iv successful immunoprecipitation of a RyR-calsenilin protein complex from brain tissue provided evidence of a functional interaction. Using electrophysiological and Ca2+ imaging techniques the modulatory effects of calsenilin on Ca2+ release in a single RyR channel or in a cellular system with a population of RyR channels, respectively, whereby RyR-mediated intracellular Ca2+ release by calsenilin was determined under physiological and pathophysiological intracellular Ca2+ concentrations. Calsenilin directly interacts with the RyR, modulating Ca2+ induced Ca2+ release (CICR) pathways in neuronal cells. Further characterization of this interaction and its pharmacological and molecular biological control could provide insight into altered Ca2+ signaling in neurodegenerative and other diseases controlled by CICR and aid in developing novel alternative therapies using these newly identified mechanisms as targets."],"dc:identifier.uri":["https://hdl.handle.net/10355/45498"],"dc:language.iso":["eng"],"dc:subject":["Alzheimer's Disease","Calcium","Calsenilin","Ryanodine"],"dc:title":["Modulation of neuronal ryanodine receptor-mediated calcium signaling by calsenilin"],"dc:type":["Thesis"],"thesis:degree_discipline":["Cell Biology and Biophysics (UMKC)","Molecular Biology and Biochemistry (UMKC)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Missouri--Kansas City"]},"updated_at":"2026-07-24T05:18:49Z"}