【《微管剪切蛋白家族研究的文献综述》3000字】

微管剪切蛋白家族研究的文献综述1.1微管剪切蛋白概述微管剪切蛋白最早报道于1991年，是非洲爪蟾卵提取物ADDINEN.CITE<EndNote><Cite><Author>Vale</Author><Year>1991</Year><RecNum>228</RecNum><DisplayText>(Vale,1991)</DisplayText><record><rec-number>228</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1613648327">228</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vale,R.D.</author></authors></contributors><auth-address>DepartmentofPharmacology,UniversityofCalifornia,SanFrancisco94143.</auth-address><titles><title>SeveringofstablemicrotubulesbyamitoticallyactivatedproteininXenopuseggextracts</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>827-39</pages><volume>64</volume><number>4</number><edition>1991/02/22</edition><keywords><keyword>AdenylylImidodiphosphate/pharmacology</keyword><keyword>Alkaloids/pharmacology</keyword><keyword>Animals</keyword><keyword>CellCycle</keyword><keyword>EdeticAcid/pharmacology</keyword><keyword>EgtazicAcid/pharmacology</keyword><keyword>Interphase</keyword><keyword>Kinetics</keyword><keyword>Microtubules/drugeffects/physiology/*ultrastructure</keyword><keyword>Mitosis</keyword><keyword>Oocytes/*cytology/ultrastructure</keyword><keyword>Paclitaxel</keyword><keyword>Proto-OncogeneProteins/pharmacology</keyword><keyword>Proto-OncogeneProteinsc-mos</keyword><keyword>TimeFactors</keyword><keyword>Tubulin/metabolism</keyword><keyword>Xenopuslaevis</keyword></keywords><dates><year>1991</year><pub-dates><date>Feb22</date></pub-dates></dates><isbn>0092-8674(Print) 0092-8674(Linking)</isbn><accession-num>1671762</accession-num><urls><related-urls><url>/pubmed/1671762</url></related-urls></urls><electronic-resource-num>10.1016/0092-8674(91)90511-v</electronic-resource-num></record></Cite></EndNote>(Vale,1991)，随后研究人员在海胆卵中纯化出该蛋白，并且以日本武士刀的名称命名—KataninADDINEN.CITEADDINEN.CITE.DATA(McNallyandVale,1993;Vale,1991)。katanin是一种依赖ATP酶活性，具有剪切微管作用的蛋白，隶属于具有催化作用的ATPase家族ADDINEN.CITEADDINEN.CITE.DATA(Hartmanetal.,1998)。AAA（ATPasesassociatedwithdiversecellularactivities）蛋白家族是一类广泛存在于几乎所有生物体内的一类蛋白，可以利用ATP水解产生的能量参与细胞内的多种细胞生理活动，例如基因表达、细胞内膜融合和调控细胞周期等。AAA蛋白相对保守，含有200-250个氨基酸，通常可为六聚体或者十二聚体叠状环，含有ATP酶结构域，被称为AAA模块。根据AAA模块的系统发育，可以分为四组，Vps4、spastin、katanin和fidgetinADDINEN.CITE<EndNote><Cite><Author>Monroe</Author><Year>2016</Year><RecNum>1170</RecNum><DisplayText>(MonroeandHill,2016)</DisplayText><record><rec-number>1170</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1615736000">1170</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Monroe,N.</author><author>Hill,C.P.</author></authors></contributors><auth-address>UnivUtah,SchMed,DeptBiochem,SaltLakeCity,UT84112USA</auth-address><titles><title>MeioticCladeAAAATPases:ProteinPolymerDisassemblyMachines</title><secondary-title>JournalofMolecularBiology</secondary-title><alt-title>JMolBiol</alt-title></titles><alt-periodical><full-title>JMolBiol</full-title></alt-periodical><pages>1897-1911</pages><volume>428</volume><number>9</number><keywords><keyword>hereditaryspasticparaplegia</keyword><keyword>atp-dependentoligomerization</keyword><keyword>microtubule-severingenzymes</keyword><keyword>vps4stimulatoryelement</keyword><keyword>traffickingmitdomain</keyword><keyword>escrt-iiirecognition</keyword><keyword>amino-acidresidues</keyword><keyword>structuralbasis</keyword><keyword>multivesicularbody</keyword><keyword>plasma-membrane</keyword></keywords><dates><year>2016</year><pub-dates><date>May8</date></pub-dates></dates><isbn>0022-2836</isbn><accession-num>WOS:000376695100008</accession-num><urls><related-urls><url><GotoISI>://WOS:000376695100008</url></related-urls></urls><electronic-resource-num>10.1016/j.jmb.2015.11.004</electronic-resource-num><language>English</language></record></Cite></EndNote>(MonroeandHill,2016)。在这四类蛋白中，其中spastin，katanin和fidgetin可以对微管具有剪切作用。katanin，spastin和fidgetin三种剪切蛋白在结构上都相对保守并且都有类似的结构域，包括具有AAA-ATP酶活性的C端核心结构域和同微管相互作用与物质运输的Nc端结构域（MIT）ADDINEN.CITEADDINEN.CITE.DATA(HansonandWhiteheart,2005;McNallyandRoll-Mecak,2018)。图1.16剪切蛋白家族分类示例图展示了剪切家族蛋白的分类情况，主要有三类，分为katanin、spastin和figentinADDINEN.CITEADDINEN.CITE.DATA(Hartmanetal.,1998)。Spastin是首先在成人的遗传性痉挛截瘫（hereditaryspasticparaplegia，HSP）一种神经肌肉疾病的研究中发现的ADDINEN.CITEADDINEN.CITE.DATA(Lindseyetal.,2000)，该疾病的主要机制是微管剪切活性大大降低ADDINEN.CITEADDINEN.CITE.DATA(Evansetal.,2005;Hazanetal.,1999)。spastin包含AAA结构域、微管结合并行使剪切作用的微管结合结构域（MTBD）、微管作用运输结构域（MIT）和具有结合其它细胞器的跨膜结构域ADDINEN.CITEADDINEN.CITE.DATA(Roll-MecakandVale,2005;Whiteetal.,2007)。在体外实验中，该蛋白可以剪切紫杉醇稳定的微管ADDINEN.CITEADDINEN.CITE.DATA(Hazanetal.,1999)。该蛋白具有两种不同的转录本：spastinM1V和spastinM87V。spastin蛋白广泛的存在于神经元的轴突末端、纺锤体和果蝇的轴突中。而该蛋白在不同的空间和部位发挥不同功能ADDINEN.CITEADDINEN.CITE.DATA(Matsushita-Ishiodorietal.,2009)。Fidgetin是AAA超家族成员之一。Fidgetin突变小鼠是在20世纪40年代被发现的，主要表现为头部晃动、多趾、骨畸形以及内耳道减少等特征ADDINEN.CITE<EndNote><Cite><Author>Konyukhov</Author><Year>1976</Year><RecNum>1186</RecNum><DisplayText>(KonyukhovandSazhina,1976)</DisplayText><record><rec-number>1186</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1615741089">1186</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Konyukhov,B.V.</author><author>Sazhina,M.V.</author></authors></contributors><titles><title>Thecellcycleandretinalhistogenesisfidgetmutantmice</title><secondary-title>DevBiol</secondary-title></titles><periodical><full-title>DevBiol</full-title></periodical><pages>13-22</pages><volume>54</volume><number>1</number><edition>1976/11/01</edition><keywords><keyword>Animals</keyword><keyword>*CellDifferentiation</keyword><keyword>CellDivision</keyword><keyword>Chromosomes</keyword><keyword>DNA/metabolism</keyword><keyword>Female</keyword><keyword>*Genes,Recessive</keyword><keyword>Homozygote</keyword><keyword>Mice</keyword><keyword>Mutation</keyword><keyword>Pregnancy</keyword><keyword>Retina/cytology/*growth&development/metabolism</keyword><keyword>TimeFactors</keyword></keywords><dates><year>1976</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0012-1606(Print) 0012-1606(Linking)</isbn><accession-num>1001817</accession-num><urls><related-urls><url>/pubmed/1001817</url></related-urls></urls><electronic-resource-num>10.1016/0012-1606(76)90282-7</electronic-resource-num></record></Cite></EndNote>(KonyukhovandSazhina,1976)。研究人员一直到2000年成功基因测序后发现是AAA酶缺失所导致ADDINEN.CITE<EndNote><Cite><Author>Cox</Author><Year>2000</Year><RecNum>1187</RecNum><DisplayText>(Coxetal.,2000)</DisplayText><record><rec-number>1187</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1615741167">1187</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cox,G.A.</author><author>Mahaffey,C.L.</author><author>Nystuen,A.</author><author>Letts,V.A.</author><author>Frankel,W.N.</author></authors></contributors><auth-address>TheJacksonLaboratory,BarHarbor,Maine,USA.</auth-address><titles><title>ThemousefidgetingenedefinesanewroleforAAAfamilyproteinsinmammaliandevelopment</title><secondary-title>NatGenet</secondary-title></titles><periodical><full-title>NatGenet</full-title></periodical><pages>198-202</pages><volume>26</volume><number>2</number><edition>2000/10/04</edition><keywords><keyword>AdenosineTriphosphatases/chemistry/*genetics</keyword><keyword>AminoAcidSequence</keyword><keyword>Animals</keyword><keyword>*ChromosomeMapping</keyword><keyword>*EmbryonicandFetalDevelopment</keyword><keyword>Evolution,Molecular</keyword><keyword>Exons</keyword><keyword>GeneExpressionRegulation,Developmental</keyword><keyword>GeneticMarkers</keyword><keyword>Heterozygote</keyword><keyword>Homozygote</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice,NeurologicMutants/*genetics</keyword><keyword>MolecularSequenceData</keyword><keyword>Phylogeny</keyword><keyword>*Polymorphism,Genetic</keyword><keyword>SequenceAlignment</keyword><keyword>SequenceHomology,AminoAcid</keyword></keywords><dates><year>2000</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1061-4036(Print) 1061-4036(Linking)</isbn><accession-num>11017077</accession-num><urls><related-urls><url>/pubmed/11017077</url></related-urls></urls><electronic-resource-num>10.1038/79923</electronic-resource-num></record></Cite></EndNote>(Coxetal.,2000)。因此命名为fidgetin。细胞内实验证明该蛋白在有丝分裂过程中通spastin是共定位。通过对该蛋白表达纯化发现，在体外情况下，可以剪切微管ADDINEN.CITEADDINEN.CITE.DATA(Mukherjeeetal.,2012)。在果蝇S2细胞中，spastin和fidgetin可能产生同在植物皮层细胞中类似的现象，即在γ-TuRCs末端打开微管负端的现象，但是这样的事件并没有被观察到，因为在纺锤体极微管密度太高，无法扑捉到相应的图像。非常有趣的是，当在S2细胞中过表达fidgetin时，并不会导致细胞中的微管解体，而纯化的fidgetin蛋白在体外实验中尚被证明可以切断微管。Katanin蛋白是由具有AAA-ATP酶催化活性的p60亚基和有识别位点作用的p80亚基所组成的稳定复合物ADDINEN.CITEADDINEN.CITE.DATA(Hartmanetal.,1998)。p60亚基主要行使剪切功能，该结构为六聚体结构，单独具有活性；p80亚基主要是引导katanin稳定复合物向中心体运动ADDINEN.CITE<EndNote><Cite><Author>Ghosh</Author><Year>2012</Year><RecNum>370</RecNum><DisplayText>(Ghoshetal.,2012)</DisplayText><record><rec-number>370</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1613726871">370</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ghosh,D.K.</author><author>Dasgupta,D.</author><author>Guha,A.</author></authors></contributors><auth-address>DepartmentofBiologicalSciences,IndianInstituteofScienceEducationandResearch,Kolkata,Mohanpur,Nadia741252,India.</auth-address><titles><title>Models,Regulations,andFunctionsofMicrotubuleSeveringbyKatanin</title><secondary-title>ISRNMolBiol</secondary-title></titles><periodical><full-title>ISRNMolBiol</full-title></periodical><pages>596289</pages><volume>2012</volume><edition>2012/01/01</edition><dates><year>2012</year></dates><isbn>2090-7907(Print) 2090-7907(Linking)</isbn><accession-num>27335666</accession-num><urls><related-urls><url>/pubmed/27335666</url></related-urls></urls><custom2>PMC4890891</custom2><electronic-resource-num>10.5402/2012/596289</electronic-resource-num></record></Cite></EndNote>(Ghoshetal.,2012)。p80亚基N端的WD40结构域，负责p60引向中心体，结构中还包含一个脯氨酸富集区和C端（p80-CTD）。p60蛋白亚基包含N端微管作用区，与运输相关MIT区同p80-CTD相互作用，C端是可以结合水解ATP的AAA+活性区。p60是以单体的形式结合到ADP，促使ADP转化为ATP，诱导蛋白六聚化，这是katanin在剪切蛋白过程中所必须的ADDINEN.CITEADDINEN.CITE.DATA(Hartmanetal.,1998)。在果蝇S2细胞中，spastin和fidgetin都定位于中心体微管的负端，具有解聚的作用，而katanin是在参与了微管正端的解聚作用。katanin同spastin同源性较高，具有解聚微管的功能，但是二者作用的功能区不同ADDINEN.CITEADDINEN.CITE.DATA(WenandWang,2013)。Kataninp60和p80它们广泛存在于四膜虫、衣藻和人类的真核生物中，并且在进化过程中相对保守ADDINEN.CITE<EndNote><Cite><Author>Ghosh</Author><Year>2012</Year><RecNum>370</RecNum><DisplayText>(Ghoshetal.,2012)</DisplayText><record><rec-number>370</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1613726871">370</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ghosh,D.K.</author><author>Dasgupta,D.</author><author>Guha,A.</author></authors></contributors><auth-address>DepartmentofBiologicalSciences,IndianInstituteofScienceEducationandResearch,Kolkata,Mohanpur,Nadia741252,India.</auth-address><titles><title>Models,Regulations,andFunctionsofMicrotubuleSeveringbyKatanin</title><secondary-title>ISRNMolBiol</secondary-title></titles><periodical><full-title>ISRNMolBiol</full-title></periodical><pages>596289</pages><volume>2012</volume><edition>2012/01/01</edition><dates><year>2012</year></dates><isbn>2090-7907(Print) 2090-7907(Linking)</isbn><accession-num>27335666</accession-num><urls><related-urls><url>/pubmed/27335666</url></related-urls></urls><custom2>PMC4890891</custom2><electronic-resource-num>10.5402/2012/596289</electronic-resource-num></record></Cite></EndNote>(Ghoshetal.,2012)。katanin主要通过剪切微管调控微管的动力学特征，发挥在细胞内调节微管长度、微管密度以及在细胞内的分布功能。在动物细胞有丝分裂过程中，katatin定位于纺锤体极点，并在纺锤体组织中发挥重要作用。它被认为是早期胚胎发育的重要调控因子，而katanin编码基因的隐性突变或缺失是中心体和多极纺锤体数量急剧增加的原因。这些异常过程被认为会导致严重的小头畸形或小不全脑病，这些神经发育疾病的特征是大脑小和智力迟钝ADDINEN.CITEADDINEN.CITE.DATA(Karabayetal.,2004;Leeetal.,2009;McNallyandRoll-Mecak,2018;Nakamuraetal.,2010)。此外，katanin在植物中起着至关重要的作用，可以使植物轴向光源弯曲。同时katanin被证明参与了衣藻在过渡区剪切基体过程，对于基体完成有丝分裂过程是非常重要的ADDINEN.CITE<EndNote><Cite><Author>Rasi</Author><Year>2009</Year><RecNum>1189</RecNum><DisplayText>(Rasietal.,2009)</DisplayText><record><rec-number>1189</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1615742516">1189</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Rasi,M.Q.</author><author>Parker,J.D.</author><author>Feldman,J.L.</author><author>Marshall,W.F.</author><author>Quarmby,L.M.</author></authors></contributors><auth-address>DepartmentofMolecularBiologyandBiochemistry,SimonFraserUniversity,Burnaby,BC,Canada.</auth-address><titles><title>KataninknockdownsupportsaroleformicrotubuleseveringinreleaseofbasalbodiesbeforemitosisinChlamydomonas</title><secondary-title>MolBiolCell</secondary-title></titles><periodical><full-title>MolBiolCell</full-title></periodical><pages>379-88</pages><volume>20</volume><number>1</number><edition>2008/11/14</edition><keywords><keyword>AdenosineTriphosphatases/genetics/*metabolism</keyword><keyword>Animals</keyword><keyword>*Chlamydomonasreinhardtii/cytology/metabolism</keyword><keyword>Cilia/*metabolism/ultrastructure</keyword><keyword>GeneKnockdownTechniques</keyword><keyword>Katanin</keyword><keyword>Microtubules/*metabolism/ultrastructure</keyword><keyword>Mitosis/*physiology</keyword><keyword>ProtozoanProteins/genetics/*metabolism</keyword><keyword>RNAInterference</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1939-4586(Electronic) 1059-1524(Linking)</isbn><accession-num>19005222</accession-num><urls><related-urls><url>/pubmed/19005222</url></related-urls></urls><custom2>PMC2613114</custom2><electronic-resource-num>10.1091/mbc.E07-10-1007</electronic-resource-num></record></Cite></EndNote>(Rasietal.,2009)。图1.17katanin形成的六聚体结构示意图示例图展示了katanin形成的六聚体结构，具有中心AAA结构域，呈螺旋排列。辐射臂是保守性较差的柔性linker区域和N端的MIT结构域。AAA结构域是使用单颗粒电镜技术获得，分辨率4.4Å。MIT结构域是采用核磁共振技术获得。柔性linker结构域（灰色）是没有被实验验证，结构建模来自X-ray小角衍射实验。启动子P1(绿色)，P2(蓝绿色)，P(蓝色)，P4(橙色)，P5(紫色)，P6(红色)ADDINEN.CITEADDINEN.CITE.DATA(Iwayaetal.,2010;McNallyandRoll-Mecak,2018;Zehretal.,2017)。1.2Kataninp60-like1蛋白简介kataninp60-like1基因（CG1193，FBgn0037375）是与果蝇katanin-60（kat60）高度同源的一个基因，简称kat-60L1，具有剪切催化酶作用结构域的氨基酸相似度为67%，远高于kat60和spastin之间44%的同源性，如图ADDINEN.CITEADDINEN.CITE.DATA(Sherwoodetal.,2004a;Stewartetal.,2012b)。该基因位于果蝇的三号染色体的右臂，基因全长5704bp(3R:5,781,762..5,787,465)，包含5个外显子。kat-60L1基因有8种不同的转录本，转录翻译为8种肽段蛋白；根据转录翻译后蛋白大小可以分为4类:kat-60L1-PA、kat-60L1-PF为605aa，kat-60L1-PB,kat-60L1-PC为669aa；kat-60L1-PD,kat-60L1-PH为kat-60L1-PA、kat-60L1-PF为609aa，kat-60L1-PE,kat-60L1-PG为673aa。同时根据5’UTR区的第一个外显子的大小kat-60L1可分为两种转录本，较长的称为kat-60L1-long；另一种称为kat-60L1-shortADDINEN.CITEADDINEN.CITE.DATA(Attrilletal.,2016;Comeronetal.,2012)。图1.18kat-60L1的基因组信息示意图示例图展示了kat-60L1基因有8种不同的转录本，转录翻译为8种肽段蛋白（/reports/FBgn0037375）。根据目前电镜结构数据及体外实验信息，kat-60L1具有同kat60高度类似的C端AAAATP酶结构，因此可以推断kat-60L1具有ATP结合的能力，利用自身的ATP水解酶活性，释放Pi，为剪切微管提供能量ADDINEN.CITEADDINEN.CITE.DATA(FrickeyandLupas,2004;Gaudetetal.,2011;Selcuketal.,2013)。1.3Kataninp60-like1蛋白研究进展近年对kat-60L1的功能研究主要集中在对果蝇幼虫阶段神经元的发育和重塑方面。在果蝇的变态发育过程中，幼虫阶段所建立的神经系统会被成虫特异的神经系统所取代，同时发生一种特殊的神经元剪枝（pruning）的生理过程，这对神经系统的重塑至关重要ADDINEN.CITEADDINEN.CITE.DATA(LuoandO'Leary,2005;Truman,1990)。果蝇的变态发育过程中，剪切主要发生在中枢神经系统（centralnervoussystem，CNS）和外周神经系统（peripheralnervoussystem，PNS）中，例如蘑菇体中的γ神经元的轴突和树突，IV型感觉神经元的树突ADDINEN.CITEADDINEN.CITE.DATA(Kuoetal.,2005;Schubigeretal.,1998;YuandSchuldiner,2014)。2009年，Lee等报道在果蝇幼虫IV型感觉神经元树突发生剪枝的早期阶段，可以观察到树突中微管已经开始断裂，而kat-60L1正是影响树突中微管断裂和树突剪切的关键因素。kat-60L1在成蛹后(afterpupariumformation,APF)5小时后，开始对IV型感觉神经元中的初级轴突内部微管进行剪切，破坏其固有微管的平行结构，从而导致轴突逐渐被切断，在APF16小时内，发生完剪枝过程ADDINEN.CITE<EndNote><Cite><Author>Lee</Author><Year>2009</Year><RecNum>63</RecNum><DisplayText>(Leeetal.,2009)</DisplayText><record><rec-number>63</rec-number><foreign-keys><keyapp="EN"db-id="vrwdadt98e5druedp2b5e2dc9wz2des0w22f"timestamp="1544090966">63</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lee,Hsiu-Hsiang</author><author>Jan,LilyYeh</author><author>Jan,Yuh-Nung</author></authors></contributors><titles><title>DrosophilaIKK-relatedkinaseIk2andKataninp60-like1regulatedendritepruningofsensoryneuronduringmetamorphosis</title><secondary-title>ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica</secondary-title></titles><periodical><full-title>ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica</full-title></periodical><pages>6363-6368</pages><volume>106</volume><number>15</number><dates><year>2009</year><pub-dates><date>Apr14</date></pub-dates></dates><isbn>0027-8424</isbn><accession-num>WOS:000265174600060</accession-num><urls><related-urls><url><GotoISI>://WOS:000265174600060</url><url>/content/pnas/106/15/6363.full.pdf</url></related-urls></urls><electronic-resource-num>10.1073/pnas.0902051106</electronic-resource-num></record></Cite></EndNote>(Leeetal.,2009)。2012年Stewart对果蝇的IV型感觉神经元的树突形态功能的研究中发现，当突变kat-60L1后，果蝇幼虫对机械刺激和热损伤反应能力大大下降，IV型感觉神经元的树突分支数量减少，长度变短，这同之前报道的spastin突变体中的肌神经接点和IV型感觉神经元树突中微管减少表型类似ADDINEN.CITEADDINEN.CITE.DATA(Jinushi-Nakaoetal.,2007;Sherwoodetal.,2004a)；同时活体成像标记EB1-gfp显示，kat-60L1突变体IV型感觉神经元树突分支末端微管数量减少，这些结果更进一步证明了kat-60L1是通过剪切微管，产生新的微管片段进一步调节树突末端的稳定性和复杂性，从而影响果蝇幼虫IV型感觉神经元树突的形态和功能ADDINEN.CITEADDINEN.CITE.DATA(Stewartetal.,2012b)。而katanin-like1(KATNL1)已被证明在过表达时可破坏细胞中的微管稳定(Sonbuchneretal.，2010)。参考文献Adly,N.,Alhashem,A.,Ammari,A.,andAlkuraya,F.S.(2014).CiliarygenesTBC1D32/C6orf170andSCLT1aremutatedinpatientswithOFDtypeIX.HumMutat35,36-40.Agrawal,S.,Grimaldi,D.,andFox,J.L.(2017).HalteremorphologyandcampaniformsensillaarrangementacrossDiptera.ArthropodStructDev46,215-229.Ahmad,F.J.,Yu,W.,McNally,F.J.,andBaas,P.W.(1999).Anessentialroleforkatanininseveringmicrotubulesintheneuron.JCellBiol145,305-315.Akhmanova,A.(2018).StrengtheningMicrotubulesbyCutsthatHeal.DevCell47,400-401.Andersen,R.A.,Barr,D.J.S.,Lynn,D.H.,Melkonian,M.,Moestrup,O.,andSleigh,M.A.(1991).TerminologyandNomenclatureoftheCytoskeletalElementsAssociatedwiththeFlagellarCiliaryApparatusinProtists.Protoplasma164,1-8.Attrill,H.,Falls,K.,Goodman,J