When the processes of neurons are in close proximity they effectively couple to each other in a process termed Ephaptic coupling. This coupling occurs without the membranes touching when the space between them is some...When the processes of neurons are in close proximity they effectively couple to each other in a process termed Ephaptic coupling. This coupling occurs without the membranes touching when the space between them is some tens of nanometers. If the intra-membrane spacing has a mechanical bistability, which moves the membranes closer and further apart, the Ephaptic coupling will be turned on and off allowing one neuron to read, or not read the content of the other. This paper explores the possibilities of bistable ephaptic memory element by a study of an analogous system that operates at a much larger scale, the Stereocilia of the hair cell. Published measurement of hair cell Stereocilia force/displacement function shows both a negative slope region in the displacement function and tendency to express bistability. We show here how this negative slope region can arise through the exigency of colloid forces. An explanation of Colloid Theory, presented in a graphic form, shows how a colloid force function can be modified to match the measured hair cell cilia force function. The colloid force function is modified by a limiting function resulting from Stereocilia side links, structural details that tie together the hair cell Stereocilia clusters. Understanding how a limited, simple behavior such as Stereocilia bistability functions may point to a more general understanding of how bistability may underlie other areas of living organisms such as memory and computation.展开更多
Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their...Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their roles in the stereocilia and auditory functions are not fully understood.Here,we identify Plscr5 as a downstream target of the transcription factor POU4F3 essential for hair cell function,whose mutation causes human DFNA15 deafness.Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss.Functional analyses reveal that PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes,particularly in inner hair cells,and is important for outer hair cell and stereocilia maintenance.Our findings highlight PLSCR5 as an important downstream effector of POU4F3 and regulator of phosphatidylserine externalization and membrane dynamics required for auditory functions.展开更多
Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mech...Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mechanism.To determine the role of Tprn in hearing,we generated Tprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background.We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of Tprn-null mice starting from postnatal day 30.Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts.The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings.Radixin,a protein expressed at stereocilia tapering,was abnormally dispersed along the stereocilia shafts in Tprn-null mice.The expression levels of radixin andβ-actin significantly decreased.We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet.Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet,which resulted in damage to stereociliary bundles and hearing impairments.The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79.展开更多
The stereocilia of the Organ of Corti in 4 different echolocating bats, Myotis adversus, Murina leuco-gaster, Nyctalus plancyi (Nyctalus velutinus), and Rhinolophus ferrumequinum were observed by using scanning electr...The stereocilia of the Organ of Corti in 4 different echolocating bats, Myotis adversus, Murina leuco-gaster, Nyctalus plancyi (Nyctalus velutinus), and Rhinolophus ferrumequinum were observed by using scanning electron microscopy (SEM). Stereocilia lengths were estimated for comparison with those of non-echolocating mammals. The specialized lengths of outer hair cells (OHC) stereocilia in echolocating bats were shorter than those of non-echolocating mammals. The specialized lengths of inner hair cells (IHC) stereocilia were longer than those of outer hair cells stereocilia in the Organ of Corti of echolocating bats. These characteristics of the auditory stereocilia length of echolocating bats represent the fine architecture of the electromotility process, helping to adapt to high frequency sound and echolocation.展开更多
Myosins comprise a large superfamily of adenosine triphosphatases(ATPases)that interact with actin filaments to generate motility or force.Unconventional myosins are implicated in diverse cellular processes including ...Myosins comprise a large superfamily of adenosine triphosphatases(ATPases)that interact with actin filaments to generate motility or force.Unconventional myosins are implicated in diverse cellular processes including organelle trafficking,F-actin organization and cell movement.The unconventional myosin,myosin XVA(MYO15A),is localized at the tips of stereocilia in the inner ear hair cells and plays important roles in the development and maintenance of stereocilia.Mutations in MYO15A/Myo15a genes are responsible for hearing loss DFNB3 and shaker-2 in human and mice,respectively.In the present review,we will discuss the expression and alternative splicing of the MYO15A gene,the biochemical properties of the MYO15A protein and the association of MYO15A mutations with hearing loss.We will also discuss the recent investigations into the mechanism of how MYO15A regulates stereocilia development and maintenance.At present we are just beginning to appreciate the important roles of MYO15A in stereocilia,and further investigations are warranted to fully understand them.展开更多
Deafness is the prevailing sensory impairment among humans,impacting every aspect of one's existence.Half of congenital deafness cases are attributed to genetic factors.Studies have shown that Luzp2 is expressed i...Deafness is the prevailing sensory impairment among humans,impacting every aspect of one's existence.Half of congenital deafness cases are attributed to genetic factors.Studies have shown that Luzp2 is expressed in hair cells(HCs)and supporting cells of the inner ear,but its specific role in hearing remains unclear.To determine the importance of Luzp2 in auditory function,we generated mice deficient in Luzp2.Our results revealed that Luzp2 has predominant expression within the HCs and pillar cells.However,the loss of Luzp2 did not result in any changes in auditory threshold.HCs or synapse number and HC stereocilia morphology in Luzp2 knockout mice did not show any notable distinctions.This was the first study of the role of Luzp2 in hearing in mice,and our results provide important guidance for the screening of deafness genes.展开更多
Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From t...Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.展开更多
目的观察蝙蝠耳蜗听黄斑毛细胞的特化形态结构,以探讨听黄斑区毛细胞对蝙蝠回声定位回声频率的敏锐调谐、放大和频率选择的作用。方法选用听力正常的蹄蝠(22只)、菊头蝠(64只)和犬吻蝠(10只),分别检测其ABR各频率反应阈,对耳蜗基底膜毛...目的观察蝙蝠耳蜗听黄斑毛细胞的特化形态结构,以探讨听黄斑区毛细胞对蝙蝠回声定位回声频率的敏锐调谐、放大和频率选择的作用。方法选用听力正常的蹄蝠(22只)、菊头蝠(64只)和犬吻蝠(10只),分别检测其ABR各频率反应阈,对耳蜗基底膜毛细胞进行扫描电镜和透射电镜观察。结果三种蝙蝠ABR反应阈值除最佳频率外,均在35 dB SPL以上,菊头蝠、蹄蝠、犬吻蝠反应幅值最大及最敏锐调谐频率分别为83～86、60～62、20～28 kHz。回声定位蝙蝠耳蜗听黄斑区外毛细胞胞体(OHC)呈纺锤形或烧瓶形,明显不同于非回声定位哺乳动物的长圆柱形外毛细胞形态。结论回声定位蝙蝠耳蜗听黄斑OHC的形态特化特征支持其OHC作为耳蜗阻尼机制的结论,OHC的这种形态特化与其他耳蜗微机械结构的匹配有利于耳蜗前行波的传导。展开更多
文摘When the processes of neurons are in close proximity they effectively couple to each other in a process termed Ephaptic coupling. This coupling occurs without the membranes touching when the space between them is some tens of nanometers. If the intra-membrane spacing has a mechanical bistability, which moves the membranes closer and further apart, the Ephaptic coupling will be turned on and off allowing one neuron to read, or not read the content of the other. This paper explores the possibilities of bistable ephaptic memory element by a study of an analogous system that operates at a much larger scale, the Stereocilia of the hair cell. Published measurement of hair cell Stereocilia force/displacement function shows both a negative slope region in the displacement function and tendency to express bistability. We show here how this negative slope region can arise through the exigency of colloid forces. An explanation of Colloid Theory, presented in a graphic form, shows how a colloid force function can be modified to match the measured hair cell cilia force function. The colloid force function is modified by a limiting function resulting from Stereocilia side links, structural details that tie together the hair cell Stereocilia clusters. Understanding how a limited, simple behavior such as Stereocilia bistability functions may point to a more general understanding of how bistability may underlie other areas of living organisms such as memory and computation.
基金supported by the National Natural Science Foundation of China(82171136 and 92368110 to G.W.,82201291 to G.-J.Z.,82192861 to Z.X.,81970884 and 82192862 to X.G.)the Natural Science Foundation of Jiangsu Province(BK20220188 to Q.L.,BK20220189 to G.-J.Z.)the Fundamental Research Funds for the Central Universities(021414380533 to G.W.).
文摘Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their roles in the stereocilia and auditory functions are not fully understood.Here,we identify Plscr5 as a downstream target of the transcription factor POU4F3 essential for hair cell function,whose mutation causes human DFNA15 deafness.Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss.Functional analyses reveal that PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes,particularly in inner hair cells,and is important for outer hair cell and stereocilia maintenance.Our findings highlight PLSCR5 as an important downstream effector of POU4F3 and regulator of phosphatidylserine externalization and membrane dynamics required for auditory functions.
文摘Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mechanism.To determine the role of Tprn in hearing,we generated Tprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background.We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of Tprn-null mice starting from postnatal day 30.Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts.The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings.Radixin,a protein expressed at stereocilia tapering,was abnormally dispersed along the stereocilia shafts in Tprn-null mice.The expression levels of radixin andβ-actin significantly decreased.We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet.Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet,which resulted in damage to stereociliary bundles and hearing impairments.The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79.
基金Supported by the National Natural Science Foundation of China (Grant No. 30430120) and Foundation of President of the Chinese Academy of Sciences
文摘The stereocilia of the Organ of Corti in 4 different echolocating bats, Myotis adversus, Murina leuco-gaster, Nyctalus plancyi (Nyctalus velutinus), and Rhinolophus ferrumequinum were observed by using scanning electron microscopy (SEM). Stereocilia lengths were estimated for comparison with those of non-echolocating mammals. The specialized lengths of outer hair cells (OHC) stereocilia in echolocating bats were shorter than those of non-echolocating mammals. The specialized lengths of inner hair cells (IHC) stereocilia were longer than those of outer hair cells stereocilia in the Organ of Corti of echolocating bats. These characteristics of the auditory stereocilia length of echolocating bats represent the fine architecture of the electromotility process, helping to adapt to high frequency sound and echolocation.
基金National Key Basic Research Program of China(No.2018YFC1003600)the National Natural Science Foundation of China(No.81771001)+1 种基金Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology(No.SPKLACDB-2019000)the Fundamental Research Funds of Shandong University(No.2018JC025).
文摘Myosins comprise a large superfamily of adenosine triphosphatases(ATPases)that interact with actin filaments to generate motility or force.Unconventional myosins are implicated in diverse cellular processes including organelle trafficking,F-actin organization and cell movement.The unconventional myosin,myosin XVA(MYO15A),is localized at the tips of stereocilia in the inner ear hair cells and plays important roles in the development and maintenance of stereocilia.Mutations in MYO15A/Myo15a genes are responsible for hearing loss DFNB3 and shaker-2 in human and mice,respectively.In the present review,we will discuss the expression and alternative splicing of the MYO15A gene,the biochemical properties of the MYO15A protein and the association of MYO15A mutations with hearing loss.We will also discuss the recent investigations into the mechanism of how MYO15A regulates stereocilia development and maintenance.At present we are just beginning to appreciate the important roles of MYO15A in stereocilia,and further investigations are warranted to fully understand them.
基金supported by grants from the National Natural Science Foundation of China (81970884,81900941,81970885,82371157,82171145,82271173,and 81771019)the Natural Science Foundation of Jiangsu Province (BK20190121 and BK20200133)+1 种基金the China Postdoctoral Science Foundation (2020M681555)a Distinguished Young Scholarship supported by the Medical Science and Technology Development Foundation,Nanjing Department of Health (JQX20003).
文摘Deafness is the prevailing sensory impairment among humans,impacting every aspect of one's existence.Half of congenital deafness cases are attributed to genetic factors.Studies have shown that Luzp2 is expressed in hair cells(HCs)and supporting cells of the inner ear,but its specific role in hearing remains unclear.To determine the importance of Luzp2 in auditory function,we generated mice deficient in Luzp2.Our results revealed that Luzp2 has predominant expression within the HCs and pillar cells.However,the loss of Luzp2 did not result in any changes in auditory threshold.HCs or synapse number and HC stereocilia morphology in Luzp2 knockout mice did not show any notable distinctions.This was the first study of the role of Luzp2 in hearing in mice,and our results provide important guidance for the screening of deafness genes.
基金supported by the National Natural Science Foundation of China (No. 81070794)the National Science Foundation for Young Scientists of China (No. 31100903)+3 种基金the Natural Fund Projects of Zhejiang ProvinceChina (No. Y2110399)the Ministry of Public Heath of Zhejiang ProvinceChina (No. 2009A135)
基金supported by grants from the National Basic Research Program of China(973Program)(2012CB9679002012CB967901)+3 种基金Beijing Natural Science Foundation(5122040)supported by grants from the China Postdoctoral Science Foundation(20100377920100470103)the National Natural Science Foundation of China(NSFC)(31040 038)
文摘Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.
文摘目的观察蝙蝠耳蜗听黄斑毛细胞的特化形态结构,以探讨听黄斑区毛细胞对蝙蝠回声定位回声频率的敏锐调谐、放大和频率选择的作用。方法选用听力正常的蹄蝠(22只)、菊头蝠(64只)和犬吻蝠(10只),分别检测其ABR各频率反应阈,对耳蜗基底膜毛细胞进行扫描电镜和透射电镜观察。结果三种蝙蝠ABR反应阈值除最佳频率外,均在35 dB SPL以上,菊头蝠、蹄蝠、犬吻蝠反应幅值最大及最敏锐调谐频率分别为83～86、60～62、20～28 kHz。回声定位蝙蝠耳蜗听黄斑区外毛细胞胞体(OHC)呈纺锤形或烧瓶形,明显不同于非回声定位哺乳动物的长圆柱形外毛细胞形态。结论回声定位蝙蝠耳蜗听黄斑OHC的形态特化特征支持其OHC作为耳蜗阻尼机制的结论,OHC的这种形态特化与其他耳蜗微机械结构的匹配有利于耳蜗前行波的传导。
