Lipid Raft Targeting of Desmoglein as a Mechanism for Desmosome Assembly

桥粒糖蛋白的脂筏靶向作为桥粒组装的机制

基本信息

批准号：
9241247
负责人：
Joshua David Lewis
金额：
$ 3.45万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-22 至 2017-10-03
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9241247
关键词：
Adhesives Adult Affect Architecture Binding Biology Bulla Cadherins Cell Adhesion Cell Proliferation Cell membrane Cell-Cell Adhesion Cells Cholesterol Clinical Cytokeratin filaments Data Defect Desmosomes Development Disease Dominant-Negative Mutation Down-Regulation Elements Endocytosis Epidermal Growth Factor Receptor Goals Heart Human Inherited Intercellular Junctions Intervention Kinetics Knowledge Life Maintenance Measures Mechanical Stress Mechanics Membrane Membrane Microdomains Modeling Multiprotein Complexes Mutate Mutation Organism Pathogenesis Patients Play Process Proteins Recruitment Activity Regulation Role Signal Transduction Skin Sphingolipids Syndrome Testing Tissues Transmembrane Domain Wound Healing blastocyst cell type desmocollin desmoglein disease-causing mutation effective therapy human disease keratinocyte keratinocyte differentiation loss of function mechanical force mutant novel therapeutic intervention prevent protein transport public health relevance skin disorder stem therapy design

项目摘要

DESCRIPTION (provided by applicant): Acquired and inherited skin blistering diseases are debilitating, life-altering illnesses. Many of these diseases are caused by a loss of desmosome function. Our ability to understand and design treatments for these diseases is hindered by our relatively poor understanding of basic desmosome biology. Very little is currently known about the regulation of desmosome assembly, or the means by which assembly becomes misregulated in various skin diseases. Data from our lab and others suggest desmosomes are assembled in microdomains of the plasma membrane known as lipid rafts. In order to understand the role that lipid rafts play in desmosome biology, we are examining the consequences of lipid raft association on the desmosomal cadherins known as desmogleins. We hypothesize that the desmoglein transmembrane domain targets this protein to lipid rafts, and that lipid raft association is necessary for incorporation into desmosomes and adhesive function. In our first aim, we will determine the role of lipid raft association in desmoglein function. In our second aim, we will determine how a mutation in the transmembrane domain of a desmoglein causes a human skin disease. Our long-term goal is to understand the mechanisms involved in regulating desmosomes and to identify new targets for potential intervention in pathogenesis. Resolving the mechanisms governing desmosome assembly would constitute an important advance in our understanding of cell-cell adhesion. This advance will also pave the way for new therapeutic strategies for treating an array of human skin diseases stemming from desmosomal misregulation.

描述（通过应用程序证明）：遗传和遗传的皮肤疾病是令人衰弱的，改变了生命的疾病。 Ecomes在各种皮肤上都犯有脂质的菜，脂质筏在Desmosome somal cadherin中发挥作用。在我们的第二个目标中，在脱木蛋白功能中，脱粒化和粘合剂功能。 Ofell-Cell-Cell-Cell细胞离子也将为治疗新的治疗策略铺平道路。