{"id":4857,"date":"2014-06-03T10:47:15","date_gmt":"2014-06-03T14:47:15","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?page_id=4857"},"modified":"2014-06-03T10:47:15","modified_gmt":"2014-06-03T14:47:15","slug":"degiorgis","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/riinbre\/research\/degiorgis\/","title":{"rendered":"The molecular anatomy of APP-associated axoplasmic organelles"},"content":{"rendered":"<p><strong>Investigator:<\/strong>\u00a0Joseph DeGiorgis, Providence College<\/p>\n<p><strong>Mentor:<\/strong>\u00a0Thomas Reese, National Institutes of Health<\/p>\n<p><strong>Scientific Theme:<\/strong>\u00a0Neuroscience<\/p>\n<p style=\"text-align: justify\"><strong>Abstract:\u00a0<\/strong>The amyloid precursor protein (APP) is a causitive agent in the pathogenesis of Alzheimer&#8217;s disease. This protein\u00a0contains a single transmembrane domain and associates with membrane-bound organelles. Recently, we have shown\u00a0that APP clusters on the surfaces of organelles in the squid gaint axon at a focal point between the organelles and\u00a0cellular microtubules. Interestingly, it has been proposed that APP may serve as a &#8220;trailer-hitch&#8221; linking the motor\u00a0protein kinesin to its intercellular cargo. While our results are in agreement with these findings, to date there is no direct\u00a0evidence that APP and kinesin bind to each other in a direct or even indirect manner. However, the localization of APP\u00a0to the junction between organelles and microtubules suggests that APP, like the AD protein Toa, has a microtubulebased\u00a0function. Here, we setout to determine the molecular anatomy of APP organelles in order to more accurately\u00a0define that organelles in association with APP and to begin to address the issue of kinesin and APP interaction. We\u00a0hope to determine the concentration of APP in total axoplasm as well as in axoplasmic organelle isolates. Through\u00a0biochemical purifiecation of kinesin motors we hope to determine whether APP co-purifies with motor proteins to test\u00a0the trailer-hitch hypothesis. Finally, we propose to investigate the distribution of APP at the ultrastructural electron\u00a0microscopy level to determine the subcellular distribution of APP at the vertebrate synapse and then to determine\u00a0whther APP distribution is altered during neuronal stimulation.<\/p>\n<p style=\"text-align: justify\"><strong>Human Health Relevance:\u00a0<\/strong>The amyloid precursor protein is a lead cause of Alzheimer&#8217;s disease as mutations in the APP gene lead to\u00a0heritable forms of the disorder and a fragment of APP builds up in lesions of all AD patients. Here, we\u00a0address the function of wild-type APP in hope of shedding light on its role in the pathogenesis of disease.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator:\u00a0Joseph DeGiorgis, Providence College Mentor:\u00a0Thomas Reese, National Institutes of Health Scientific Theme:\u00a0Neuroscience Abstract:\u00a0The amyloid precursor protein (APP) is a causitive agent in the pathogenesis of Alzheimer&#8217;s disease. This protein\u00a0contains a single transmembrane domain and associates with membrane-bound organelles. Recently, we have shown\u00a0that APP clusters on the surfaces of organelles in the squid gaint axon at [&hellip;]<\/p>\n","protected":false},"author":1036,"featured_media":0,"parent":40,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-twocol.php","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-4857","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4857","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/1036"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=4857"}],"version-history":[{"count":1,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4857\/revisions"}],"predecessor-version":[{"id":37808,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4857\/revisions\/37808"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/40"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=4857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}