Solving the secretory acid sphingomyelinase puzzle: Insights from lysosome‐mediated parasite invasion and plasma membrane repair

Andrews Norma W.

摘要

Abstract > Acid sphingomyelinase (ASM) is a lysosomal enzyme that cleaves the phosphorylcholine head group of sphingomyelin, generating ceramide. Recessive mutations in SMPD1 , the gene encoding ASM, cause Niemann–Pick Disease Types A and B. These disorders are attributed not only to lipid accumulation inside lysosomes but also to changes on the outer leaflet of the plasma membrane, highlighting an extracellular role for ASM. Secretion of ASM occurs under physiological conditions, and earlier studies proposed two forms of the enzyme, one resident in lysosomes and another form that would be diverted to the secretory pathway. Such differential intracellular trafficking has been difficult to explain because there is only one SMPD1 transcript that generates an active enzyme, found primarily inside lysosomes. Unexpectedly, studies of cell invasion by the protozoan parasite Trypanosoma cruzi revealed that conventional lysosomes can fuse with the plasma membrane in response to elevations in intracellular Ca 2+ , releasing their contents extracellularly. ASM exocytosed from lysosomes remodels the outer leaflet of the plasma membrane, promoting parasite invasion and wound repair. Here, we discuss the possibility that ASM release during lysosomal exocytosis, in response to various forms of stress, may represent a major source of the secretory form of this enzyme. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><abstract type=“main”xml:lang=“en”><title type=“main”>abstract>酸性鞘磷脂酶（ASM）是一种溶酶体酶，可分解鞘磷脂的磷酸胆碱头基，生成神经酰胺。编码ASM的基因SMPD1的隐性突变导致尼曼-匹克病A型和B型。这些疾病不仅归因于溶酶体内的脂质积聚，还归因于质膜外小叶的变化，突出了ASM的细胞外作用。ASM的分泌发生在生理条件下，早期的研究提出了两种形式的酶，一种存在于溶酶体中，另一种形式转移到分泌途径。这种差异性的细胞内转运很难解释，因为只有一个SMPD1转录本产生一种主要在溶酶体内发现的活性酶。出乎意料的是，对原生动物寄生虫cruzi锥虫侵入细胞的研究显示，常规溶酶体可以与质膜融合，以响应细胞内Ca2+的升高，将其内容物释放到细胞外。溶酶体分泌的ASM重塑质膜的外小叶，促进寄生虫入侵和伤口修复。在这里，我们讨论了ASM在溶酶体胞吐过程中释放的可能性，以应对各种形式的应激，可能是这种酶分泌形式的主要来源 </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-15891/'>《Cellular microbiology》</a> <b style="margin: 0 2px;">|</b><span>2019年第11期</span><b style="margin: 0 2px;">|</b><span>共7页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Andrews Norma W.&option=202" target="_blank" rel="nofollow">Andrews Norma W.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Cell Biology and Molecular GeneticsUniversity of MarylandCollege Park Maryland;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/173.html" title="普通生物学">普通生物学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=ASM&option=203" rel="nofollow">ASM;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cell injury/sublethal injury&option=203" rel="nofollow">cell injury/sublethal injury;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cell membrane&option=203" rel="nofollow">cell membrane;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=lysosome&option=203" rel="nofollow">lysosome;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=secretion&option=203" rel="nofollow">secretion;</a> </p> <div class="translation"> 机译：ASM;细胞损伤/核心损伤;细胞膜;溶酶体;分泌物; 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K.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Gately, M. K.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Mayer, M. M.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Mayer, M. M.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Henney, C. S.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Henney, C. S. </a> <span>1976</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：抗淋巴毒素对细胞介导的细胞毒性的影响：两种途径的证据，一种涉及淋巴毒素和其他需要杀手和靶细胞的质膜之间的亲密接触</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-higher-education-academic-abstracts-biology_thesis/0201255400831.html">Insights into the role of jasmonic acid-mediated defenses against necrotrophic and biotrophic fungal pathogens</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Christopher J.ANTICO&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . Christopher J.ANTICO</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chad COLON&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Chad COLON</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Taylor BANKS&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Taylor BANKS</a> <span> <a href="/journal-cn-5107/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国高等学校学术文摘·生物学 </a> </span> <span> . 2012</span><span>,第001期</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06130458417748.html">PHARMACEUTICAL ANTIALCOHOLIC COMPOSITION STIMULATING ENERGY METABOLISM, SECRETORY FUNCTION OF GASTRIC MUCOUS MEMBRANE AND PRODUCING HALIOPROTECTIVE AND ANTITUMOR EFFECT; METHOD OF PREVENTION AND TREATMENT OF ALCOHOLIC INTOXICATION AND ALCOHOLIC ABSTINENCE SYNDROME; METHOD FOR STIMULATING ENERGY METABOLISM; METHOD FOR STIMULATING AND DIAGNOSING ACID-FORMING AND SECRETORY FUNCTIONS OF GASTRIC MUCOSA; METHOD FOR PROTECTING WARM-BLOODED ANIMALS FROM RADIATION INJURY</a> <b>[P]</b> . <span> 外国专利：  RU2039556C1 </span> <span> . 1995-07-20</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：药物抗胆汁成分刺激能量代谢，胃粘膜膜的分泌功能以及产生盐的保护和反作用;预防和治疗酒精中毒和酒精戒断综合征的方法;刺激能量代谢的方法;一种刺激和诊断胃粘膜酸形成和分泌功能的方法;防止辐射伤害的温血动物的方法 </span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06130448216516.html">Non-invasive determination of mediator synthesis capacity of living being, comprising applying covered, stimulant-carrying membrane to living body surface, later determining concentration of mediator liberated</a> <b>[P]</b> . <span> 外国专利：  DE19935523A1 </span> <span> . 2001-02-15</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：非侵入性确定生物介体合成能力的方法，包括在生物体表面上覆盖有刺激剂的覆盖膜，随后确定释放的介体浓度 </span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130501338409.html">USE OF RECOMBINANT HUMAN ACID SPHINGOMYELINASE TO IMPROVE SKELETAL MYOFIBER REPAIR</a> <b>[P]</b> . <span> 外国专利：  WO2022006058A1 </span> <span> . 2022-01-06</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：使用重组人酸鞘氨基氨基酶改善骨骼肌电纤维修复 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" 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