CYTOSKELETAL TARGETS OF NEURONAL/TESTICULAR TOXICANTS

一组大容量、商业上重要的环境和 工业毒物-包括丙烯酰胺、有机磷 酯类和六碳类-选择性地伤害神经系统 男性生殖系统 在这个实验室里的研究， 由题为“环境/工业”的ROl ES 05033支持 毒物和睾丸损伤”，并通过1993年8月31日资助， 专注于睾丸支持细胞细胞骨架作为靶点， 这些毒物。 研究职业发展奖提供 有机会扩大研究范围，强调 多方面的方法来调查这些合并的 神经元/睾丸毒物。 候选人，医学博士金·伯克海德，哲学博士、是助理教授 病理学和实验室医学系 在布朗大学。 接受研究职业发展 奖励将解除他与研究无关的行政和 教学负担，目前占据了他50%的时间。 的 我的期望是，Boekelheide博士将继续利用 优秀的基础科学研究，并在他的进步 布朗大学的研究生涯。 一份手稿最近被接受发表在《纽约时报》上， 细胞生物学（医学博士）Neely和K. Boekelheide，“支持细胞 突起具有轴质特征：一个有序的微管 分布和丰富的高分子量微管 相关蛋白（细胞质动力蛋白）”），描述了 采用比较方法来阐明神经元的共同特征 和睾丸细胞骨架。 该提案将继续 常见细胞骨架特征的基本描述和检查 独特的神经元/睾丸细胞骨架成分作为靶点， 毒物引起的损伤 以下具体假设将 测试：1）中毒与一些有毒物质抑制 支持细胞中发现的细胞质动力蛋白的功能， 轴突，2）抑制这种微管马达的功能 阻断轴突中的逆行运输和 支持细胞; 3）轴突逆行运输失败 导致局部轴突病变， 支持细胞囊泡转运失败导致的变性 生殖细胞坏死和脱落

A group of large volume, commercially important environmental and industrial toxicants - including the acrylamides, organophosphorus esters and the hexacarbons - selectively injure the nervous system and male reproductive system. Research in this laboratory, supported by ROl ES05033 entitled "Environmental/Industrial Toxicants and Testicular Injury" and funded through 08/31/93, has focused on the testicular Sertoli cell cytoskeleton as a target for these toxicants. A Research Career Development Award provides an opportunity to expand the scope of research by emphasizing a multifaceted approach to they investigation of these combined neuronal/testicular toxicants. The candidate, Kim Boekelheide, M.D., Ph.D., is Assistant Professor (tenure track} the Department of Pathology and Laboratory Medicine at Brown University. Receipt of a Research Career Development Award will relieve him of non-research-related administrative and teaching burdens which currently occupy 50% of his time. The expectation is that Dr. Boekelheide will continue to take advantage of the fine basic science research available and advance in his research career at Brown University. A manuscript recently accepted for publication in The Journal of Cell biology (M.D. Neely and K. Boekelheide, "Sertoli cell processes have axoplasmic features: an ordered microcubule distribution and an abundance high molecular weight microtubule associated protein (cycoplasmic dynein)"), describes the comparative approach taken to elucidate shared features of neuronal and testicular cytoskeletons. This proposal will continue the basic description of common cytoskeletal features and examine unique neuronal/ testicular cytoskeletal components as targets for toxicant-induced injury. The following specific hypothesis will be tested: 1) intoxication with some toxicants inhibits the function of the cytoplasmic dynein found in Sertoli cells and axons, 2) inhibition of the function of this microtubule motor blocks retrograde transport in the axon and vesicle transport in the Sertoli cell, and 3) failure of retrograde axonal transport results in a localized axonopathy with associated distal degeneration while failure of Sertoli cell vesicle transport leads to germ cell necrosis and sloughing.