4.6 Article

A Novel Ion Channel Formed by Interaction of TRPML3 with TRPV5

期刊

PLOS ONE
卷 8, 期 2, 页码 -

出版社

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0058174

关键词

-

资金

  1. National Institutes of Health [R01 DC004563, P30 DC010363]

向作者/读者索取更多资源

TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Cell Biology

ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points

Jocelyn F. Krey, Chang Liu, Inna A. Belyantseva, Michael Bateschell, Rachel A. Dumont, Jennifer Goldsmith, Paroma Chatterjee, Rachel S. Morrill, Lev M. Fedorov, Sarah Foster, Jinkyung Kim, Alfred L. Nuttall, Sherri M. Jones, Dongseok Choi, Thomas B. Friedman, Anthony J. Ricci, Bo Zhao, Peter G. Barr-Gillespie

Summary: The stereocilia rootlet plays a critical role in protecting vertebrate hair cells from overstimulation. This study demonstrates that the ANKRD24 protein concentrates at the insertion point of the stereocilia, forming a ring and binding with TRIOBP-5 to maintain its distribution. ANKRD24 and TRIOBP-5 together organize the rootlets, enabling long-term auditory resilience.

JOURNAL OF CELL BIOLOGY (2022)

Article Multidisciplinary Sciences

In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective

Jinkyung Kim, Anthony J. Ricci

Summary: This study tracks the entry and targeting process of a commonly used antibiotic, aminoglycosides (AGs), in the cochlea. The authors found that AGs enter the cochlea through the stria vascularis and selectively target cochlear sensory hair cells (HCs). They also identified the mechanotransducer channel and megalin as key factors in AG uptake. Blocking megalin prevented AG accumulation in HCs and reduced HC degeneration and hearing loss.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

Article Multidisciplinary Sciences

Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice

Barbara Spix, Elisabeth S. Butz, Cheng-Chang Chen, Anna Scotto Rosato, Rachel Tang, Aicha Jeridi, Veronika Kudrina, Eva Plesch, Philipp Wartenberg, Elisabeth Arlt, Daria Briukhovetska, Meshal Ansari, Gizem Gunes Gunsel, Thomas M. Conlon, Amanda Wyatt, Sandra Wetzel, Daniel Teupser, Lesca M. Holdt, Fabien Ectors, Ingrid Boekhoff, Ulrich Boehm, Jaime Garcia-Anoveros, Paul Saftig, Martin Giera, Sebastian Kobold, Herbert B. Schiller, Susanna Zierler, Thomas Gudermann, Christian Wahl-Schott, Franz Bracher, Ali Oender Yildirim, Martin Biel, Christian Grimm

Summary: The study reveals TRPML3 as a key regulator of MMP-12 clearance by alveolar macrophages, suggesting it as a therapeutic target for emphysema and chronic obstructive pulmonary disease.

NATURE COMMUNICATIONS (2022)

Review Cell Biology

Endolysosomal Cation Channels and Lung Disease

Barbara Spix, Aicha Jeridi, Meshal Ansari, Ali Oender Yildirim, Herbert B. Schiller, Christian Grimm

Summary: Endolysosomal cation channels, such as TRPML3, P2X4, TRPM2, TRPV2, and TRPA1, play important roles in lung diseases such as emphysema and chronic obstructive pulmonary disease (COPD). These channels are involved in various physiological processes in the lung and understanding their functions can provide insights into lung disease.
Article Neurosciences

Identifying targets to prevent aminoglycoside ototoxicity

Jinkyung Kim, Sriram Hemachandran, Alan G. Cheng, Anthony J. Ricci

Summary: Aminoglycosides are potent antibiotics commonly prescribed worldwide, but their use carries the risk of ototoxicity and there are currently no approved antidotes. Therefore, it is important to review recent advances in understanding aminoglycoside ototoxicity and potential intervention sites for preventing ototoxicity.

MOLECULAR AND CELLULAR NEUROSCIENCE (2022)

Article Medicine, Research & Experimental

TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann-Pick type C1, and Batten disease

Anna Scotto Rosato, Einar K. Krogsaeter, Dawid Jaslan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Boeck, Amanda Wyatt, Daniela Wuenkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber-Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl-Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L. Medina, Dominik Paquet, Christian Grimm

Summary: This study found that TPC2 activation can improve cellular phenotypes associated with LSDs, including cholesterol or lipofuscin accumulation and abnormal vacuole formation. Validation in patient cells and mouse models suggests that TPC2 is a promising target for the treatment of different types of LSDs.

EMBO MOLECULAR MEDICINE (2022)

Article Multidisciplinary Sciences

Segregated cation flux by TPC2 biases Ca2+ signaling through lysosomes

Yu Yuan, Dawid Jaslan, Taufiq Rahman, Stephen R. Bolsover, Vikas Arige, Larry E. Wagner, Carla Abrahamian, Rachel Tang, Marco Keller, Jonas Hartmann, Anna S. Rosato, Eva-Maria Weiden, Franz Bracher, David Yule, Christian Grimm, Sandip Patel

Summary: This study reveals that TPC2 can selectively increase its permeability to calcium ions when co-activated by the endogenous ligands NAADP and PI(3,5)P-2. This finding indicates that the flux of different ions through the same channel can be independently controlled and identifies TPC2 as a potential coincidence detector that optimizes lysosomal calcium signaling.

NATURE COMMUNICATIONS (2022)

Article Multidisciplinary Sciences

CLN3 is required for the clearance of glycerophosphodiesters from lysosomes

Nouf N. Laqtom, Wentao Dong, Uche N. Medoh, Andrew L. Cangelosi, Vimisha Dharamdasani, Sze Ham Chan, Tenzin Kunchok, Caroline A. Lewis, Ivonne Heinze, Rachel Tang, Christian Grimm, An N. Dang Do, Forbes D. Porter, Alessandro Ori, David M. Sabatini, Monther Abu-Remaileh

Summary: Lysosomes play crucial roles in cellular function, and dysfunction is associated with various human diseases. The study reveals the importance of CLN3 protein in glycerophospholipid metabolism within lysosomes, as its loss leads to massive accumulation of GPDs.

NATURE (2022)

Article Biochemical Research Methods

A chemo-mechanical cochleostomy preserves hearing for the in vivo functional imaging of cochlear cells

Jinkyung Kim, Anthony J. Ricci

Summary: This article introduces a surgical procedure that allows effective imaging of cochlear cells in hearing mice, while preserving hearing thresholds. This technique may enable real-time tracking of ototoxic drug transport into the cochleae and monitoring of sound-evoked functional activity in multiple cochlear cells. It may also have implications for improving cochlear implantation in humans.

NATURE PROTOCOLS (2023)

Article Multidisciplinary Sciences

Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion

Lora L. Martucci, Jean-Marie Launay, Natsuko Kawakami, Cecile Sicard, Nathalie Desvignes, Mbarka Dakouane-Giudicelli, Barbara Spix, Maude Tetu, Franck -Olivier Gilmaire, Sloane Paulcan, Jacques Callebert, Cyrille Vaillend, Franz Bracher, Christian Grimm, Philippe Fossier, Sabine de la Porte, Hirotaka Sakamoto, John Morris, Antony Galione, Sylvie Granon, Jose-Manuel Cancela

Summary: Oxytocin is released in response to Ca2+ influx and release from intracellular stores, both critical for priming large dense-cored vesicles in hypothalamic neurons for exocytosis. This study shows that lysosomes surround dendritic vesicles and activation of endolysosomal two-pore channels (TPCs) provides the necessary Ca2+ signals to prime oxytocin release. TPC knockout mice and mice lacking TPC exhibit impaired oxytocin secretion and social behavior, which can be restored by direct administration of oxytocin.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

Article Cell Biology

GIPC3 couples to MYO6 and PDZ domain proteins, and shapes the hair cell apical region

Paroma Chatterjee, Clive P. Morgan, Jocelyn F. Krey, Connor Benson, Jennifer Goldsmith, Michael Bateschell, Anthony J. Ricci, Peter G. Barr-Gillespie

Summary: GIPC3 is initially localized to the cytoplasm of hair cells in the cochlea and then concentrated at cell junctions during postnatal development. Gipc3K & DEG;/K & DEG; mice have normal mechanotransduction currents but lack auditory brainstem response. The disruption of cell junctions and altered distribution of GIPC3 suggest that GIPC3 and MYO6 play a role in shaping the cuticular plate.

JOURNAL OF CELL SCIENCE (2023)

Article Neurosciences

Coupling between the Stereocilia of Rat Sensory Inner-Hair-Cell Hair Bundles Is Weak, Shaping Their Sensitivity to Stimulation

Alexandra L. Scharr, Daibhid O. Maoileidigh, Anthony J. Ricci

Summary: The hair bundle, composed of mechanically coupled stereocilia, is a universal mechanosensory organelle in auditory, vestibular, and lateral-line systems. The dynamics of individual stereocilia in response to bundle stimulus has not been quantified. By stimulating and tracking individual inner-hair-cell stereocilia, it was found that nonuniform stimulation led to dissimilar stereociliary displacements and stereocilia closer to the stimulator moved more. The weak coupling between stereocilia suggests that more uniform stimulation across the tallest stereocilia is required to enhance the receptor current.

JOURNAL OF NEUROSCIENCE (2023)

Meeting Abstract Biophysics

Cholesterol as a tool to probe the role of membrane in cochlear hair cell mechanotransduction

Shefin Sam George, Thomas Effertz, Anthony J. Ricci

BIOPHYSICAL JOURNAL (2023)

Meeting Abstract Biophysics

Tmc regulates membrane viscosity in mammalian cochlear hair cells

Shefin Sam George, Amel El Bahloul-Jaziri, Anthony J. Ricci

BIOPHYSICAL JOURNAL (2023)

Meeting Abstract Biophysics

The functional role of connectors in outer-hair-cell hair bundles

Zenghao Zhu, Anthony J. Ricci, Daibhid O. Maoileidigh

BIOPHYSICAL JOURNAL (2022)

暂无数据