AP180 promotes release site clearance and clathrin-dependent vesicle reformation in mouse cochlear inner hair cells

Kroll, Jana; Özçete, Özge Demet; Jung, Sangyong; Maritzen, Tanja; Milošević, Ira; Wichmann, Carolin; Moser, Tobias

doi:10.1242/jcs.236737

Cited by 16 publications

(16 citation statements)

References 65 publications

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“…As outlined in the introduction, the synaptic ribbon has a well-established role in synaptic vesicle exocytosis (for review, [ 26 , 28 , 32 ]). The synaptic ribbon is affected by mutations of endocytic proteins [ 33 , 34 , 35 ] and might thus also play a role in endocytic vesicle retrieval (e.g., [ 28 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]). Therefore, we analyzed in detail whether the alterations of synaptic ribbons are associated with changes in evoked and basal synaptic vesicle cycling.…”

Section: Resultsmentioning

confidence: 99%

Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic Ribbon Size and Reduced Ribbon-Associated Vesicle Pools in Rod Photoreceptor Synapses

Kesharwani

Schwarz

Dembla

et al. 2021

IJMS

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Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that finally leads to demyelination. Demyelinating optic neuritis is a frequent symptom in MS. Recent studies also revealed synapse dysfunctions in MS patients and MS mouse models. We previously reported alterations of photoreceptor ribbon synapses in the experimental auto-immune encephalomyelitis (EAE) mouse model of MS. In the present study, we found that the previously observed decreased imunosignals of photoreceptor ribbons in early EAE resulted from a decrease in synaptic ribbon size, whereas the number/density of ribbons in photoreceptor synapses remained unchanged. Smaller photoreceptor ribbons are associated with fewer docked and ribbon-associated vesicles. At a functional level, depolarization-evoked exocytosis as monitored by optical recording was diminished even as early as on day 7 after EAE induction. Moreover compensatory, post-depolarization endocytosis was decreased. Decreased post-depolarization endocytosis in early EAE correlated with diminished synaptic enrichment of dynamin3. In contrast, basal endocytosis in photoreceptor synapses of resting non-depolarized retinal slices was increased in early EAE. Increased basal endocytosis correlated with increased de-phosphorylation of dynamin1. Thus, multiple endocytic pathways in photoreceptor synapse are differentially affected in early EAE and likely contribute to the observed synapse pathology in early EAE.

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Section: Resultsmentioning

confidence: 99%

Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic Ribbon Size and Reduced Ribbon-Associated Vesicle Pools in Rod Photoreceptor Synapses

Kesharwani

Schwarz

Dembla

et al. 2021

IJMS

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“…In an integrated analysis of whole exome sequencing and copy number evaluation in Parkinson's disease (PD), loss of function and missense changes in SNAP91 were observed in PD patients (Yemni et al, 2019). SNAP91 was also found to promote release site clearance and clathrin-dependent vesicle reformation in mouse cochlear inner hair cells (Kroll et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis

Hu¹,

Zhou³

et al. 2020

Front. Aging Neurosci.

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Background: The pathogenesis of Alzheimer’s disease (AD) remains to be elucidated. This study aimed to identify the hub genes in AD pathogenesis and determine their functions and pathways.Methods: A co-expression network for an AD gene dataset with 401 samples was constructed, and the AD status-related genes were screened. The hub genes of the network were identified and validated by an independent cohort. The functional pathways of hub genes were analyzed.Results: The co-expression network revealed a module that related to the AD status, and 101 status-related genes were screened from the trait-related module. Gene enrichment analysis indicated that these status-related genes are involved in synaptic processes and pathways. Four hub genes (ENO2, ELAVL4, SNAP91, and NEFM) were identified from the module, and these hub genes all participated in AD-related pathways, but the associations of each gene with clinical features were variable. An independent dataset confirmed the different expression of hub genes between AD and controls.Conclusions: Four novel genes associated with AD pathogenesis were identified and validated, which provided novel therapeutic targets for AD.

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“…In addition to neuronal and lymphocyte phenotypes for CLCa or CLCb depletion [15,62] and the muscle phenotypes for defective CHC splicing [33,34], mutation in the AAGAB protein affecting AP2 assembly manifests as the human skin disease punctate palmoplantar keratoderma type 1 [40] and AP1 mutations are associated with congenital enteropathy [63]. Deficiency of the CME-nucleating protein FCHO1 causes a T-lymphocyte defect [64], and loss of the assembly regulator AP180 affects murine cochlear inner hair cells [65] in addition to neuronal function, and the latter is seen for many other adaptor and assembly factor defects [66]. Interestingly, degenerative diseases in which protein aggregates (Tau or -synuclein) sequester the Hsc70 clathrin uncoating protein have phenotypes resulting from disrupted CME that can be rescued by excess Hsc70 [67,68].…”

Section: Outstanding Questions In the Field: The (Disease) Devil Is In The Detailsmentioning

confidence: 99%

Clathrin’s life beyond 40: Connecting biochemistry with physiology and disease

Briant

Redlingshöfer

Brodsky

2020

Current Opinion in Cell Biology

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Understanding of the range and mechanisms of clathrin functions has developed exponentially since clathrin's discovery in 1975. Here, newly established molecular mechanisms that regulate clathrin activity and connect clathrin pathways to differentiation, disease and physiological processes such as glucose metabolism are reviewed. Diversity and commonalities of clathrin pathways across the tree of life reveal species-specific differences enabling functional plasticity in both membrane traffic and cytokinesis. New structural information on clathrin coat formation and cargo interactions emphasizes the interplay between clathrin, adaptor proteins, lipids and cargo, and how this interplay regulates quality control of clathrin function and is compromised in infection and neurological disease. Roles for balancing clathrin-mediated cargo transport are defined in stem cell development and additional disease states.

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AP180 promotes release site clearance and clathrin-dependent vesicle reformation in mouse cochlear inner hair cells

Abstract: The neuronal endocytic adaptor protein AP180 plays a dual role in inner hair cells of the murine cochlea: it is required for clearance of release sites and for membrane retrieval.

Cited by 16 publications

References 65 publications

Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic Ribbon Size and Reduced Ribbon-Associated Vesicle Pools in Rod Photoreceptor Synapses

Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic Ribbon Size and Reduced Ribbon-Associated Vesicle Pools in Rod Photoreceptor Synapses

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis

Clathrin’s life beyond 40: Connecting biochemistry with physiology and disease

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