Synaptojanin and Endophilin Mediate Neck Formation during Ultrafast Endocytosis

Watanabe, Shigeki; Mamer, Lauren; Raychaudhuri, Sumana; Luvsanjav, Delgermaa; Eisen, Julia N.; Trimbuch, Thorsten; Söhl-Kielczynski, Berit; Fenske, Pascal; Milošević, Ira; Rosenmund, Christian; Jørgensen, Erik M.

doi:10.1016/j.neuron.2018.06.005

Cited by 99 publications

(132 citation statements)

References 72 publications

(153 reference statements)

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“…However, the Drosophila model revealed loss of dopaminergic neurons, providing evidence for the contribution of synaptic autophagy defects in pathogenesis of PD (Vanhauwaert et al ). Considering its dual enzymatic activity, SynJ1 is also believed to play a role in fast endophilin‐mediated, clathrin‐independent endocytosis which is an alternative to CME (Watanabe et al ) and several other processes. It remains to be determined if SYNJ1 exert its effects on PD pathogenesis through any of the alternative endocytic pathways.…”

Section: Clathrin‐mediated Synaptic Vesicle Endocytosis: a Prime Target?mentioning

confidence: 99%

Role of the endolysosomal system in Parkinson’s disease

Vidyadhara

Lee

Chandra

2019

Journal of Neurochemistry

111

105

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Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, affecting 1–1.5% of the total population. While progress has been made in understanding the neurodegenerative mechanisms that lead to cell death in late stages of PD, mechanisms for early, causal pathogenic events are still elusive. Recent developments in PD genetics increasingly point at endolysosomal (E‐L) system dysfunction as the early pathomechanism and key pathway affected in PD. Clathrin‐mediated synaptic endocytosis, an integral part of the neuronal E‐L system, is probably the main early target as evident in auxilin, RME‐8, and synaptojanin‐1 mutations that cause PD. Autophagy, another important pathway in the E‐L system, is crucial in maintaining proteostasis and a healthy mitochondrial pool, especially in neurons considering their inability to divide and requirement to function an entire life‐time. PINK1 and Parkin mutations severely perturb autophagy of dysfunctional mitochondria (mitophagy), both in the cell body and synaptic terminals of dopaminergic neurons, leading to PD. Endolysosomal sorting and trafficking is also crucial, which is complex in multi‐compartmentalized neurons. VPS35 and VPS13C mutations noted in PD target these mechanisms. Mutations in GBA comprise the most common risk factor for PD and initiate pathology by compromising lysosomal function. This is also the case for ATP13A2 mutations. Interestingly, α‐synuclein and LRRK2, key proteins involved in PD, function in different steps of the E‐L pathway and target their components to induce disease pathogenesis. In this review, we discuss these E‐L system genes that are linked to PD and how their dysfunction results in PD pathogenesis. This article is part of the Special Issue “Synuclein”.

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Section: Clathrin‐mediated Synaptic Vesicle Endocytosis: a Prime Target?mentioning

confidence: 99%

Role of the endolysosomal system in Parkinson’s disease

Vidyadhara

Lee

Chandra

2019

Journal of Neurochemistry

111

105

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“…Although a central role of CME in synaptic vesicle protein retrieval from the plasma membrane was proposed , later research revealed that CME is not essential for the maintenance of synaptic vesicles and neurotransmission . Furthermore, fast acting recycling mechanisms have been shown to be clathrin‐independent in neurons as well as in other mammalian cells . Nevertheless, CME plays a key role in regenerating synaptic vesicles from synaptic endosomes after ultrafast endocytosis (UFE) and bulk endocytosis (but also see [PMID 24963135]).…”

Section: Synaptic Vesicle Endocytic Pathways and Their Regulation By mentioning

confidence: 99%

“…This pathway operates at a faster pace than CME (a few seconds compared to 30 s to a minute) and it has been termed fast endophilinmediated endocytosis (FEME, [54,64]) in non-neuronal mammalian cells. Endophilins, and possibly FEME, also regulate the number of synaptic vesicles and synaptic vesicle endocytosis at peripheral (neuromuscular junction) and central (hippocampal) synapses [53,57,65]. During UFE, endophilin works together with synaptojanin to accelerate the speed of endocytosis via regulation of neck formation in membrane invaginations and subsequently they regulate clathrin uncoating after vesicle reformation for synaptic endosomes [53] (also see [57,65]).…”

Section: Synaptic Vesicle Endocytic Pathways and Their Regulation By mentioning

confidence: 99%

“…Endophilins, and possibly FEME, also regulate the number of synaptic vesicles and synaptic vesicle endocytosis at peripheral (neuromuscular junction) and central (hippocampal) synapses [53,57,65]. During UFE, endophilin works together with synaptojanin to accelerate the speed of endocytosis via regulation of neck formation in membrane invaginations and subsequently they regulate clathrin uncoating after vesicle reformation for synaptic endosomes [53] (also see [57,65]). Through their roles in synaptic vesicle endocytosis, synaptojanin and endophilin help sustain the efficiency of neurotransmission during prolonged high frequency stimulation at the neuromuscular junction, even at room temperature [66].…”

Section: Synaptic Vesicle Endocytic Pathways and Their Regulation By mentioning

confidence: 99%

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Time course and temperature dependence of synaptic vesicle endocytosis

Chanaday

Kavalali

2018

FEBS Letters

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In presynaptic nerve terminals, synaptic vesicles are recycled locally via an evolutionarily conserved process that ensures maintenance of neurotransmission as well as structural integrity of synapses. Temperature is a key environmental factor that impacts critical steps involved in fusion, endocytosis and transport in different vesicle trafficking pathways. In neurons, temperature changes have been shown to impact synaptic vesicle recycling and synaptic efficacy. But contrary to non‐neuronal systems, the temperature dependence of the steps involved in fusion, endocytosis and recycling of synaptic vesicles in presynaptic terminals is not completely understood, and the existing data remain highly debated. In this Review, we discuss the implications of biophysical, biochemical and functional findings on temperature dependence of membrane retrieval in multiple systems. We propose that systematic investigation of the temperature dependence of the presynaptic vesicle trafficking process can provide novel insight into poorly understood mechanisms that govern synaptic vesicle trafficking under diverse physiological conditions.

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“…A was first attributed to play a role in fast bulk endocytosis, but with slower kinetics than that of 471 ultrafast endocytosis (Watanabe & Boucrot, 2017). More recently, endophilin A and synaptojanin were 472 found to accelerate ultrafast endocytosis at hippocampal synapses (Watanabe et al, 2018). In Cm 473 recordings of endophilin A knock-out IHCs no apparent increase in Cm was observed (Kroll et al, 2019), 474 seemingly arguing against an involvement of endophilin A in ultrafast endocytosis at this synapse.…”

Section: What Other Molecular Players Could Be Involved In Ultrafast mentioning

confidence: 99%

PKCα-dependent interaction of otoferlin and calbindin: evidence for regulation of endocytosis in inner hair cells

Cepeda

Al-Moyed

Lenz

et al. 2019

Preprint

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24Otoferlin is essential for the fast and indefatigable release of synaptic vesicles at auditory inner hair 25 cell (IHC) ribbon synapses, being involved in exocytic, endocytic and regenerative steps of the synaptic 26 vesicle cycle. Serving diverse functions at this highly dynamic synapse implies that this multi-C2 domain 27 protein is precisely regulated. Here we found protein kinase C  (PKC) and otoferlin to colocalize in 28 endocytic recycling compartments upon IHC depolarization and to interact in an activity-dependent 29 manner. In vitro assays confirmed that PKC can phosphorylate otoferlin at five serine residues, which 30 correlates with increased serine phosphorylation in <40 nm proximity to otoferlin in murine IHCs that 31 can be fully blocked by combining PKC and CaMKII inhibitors. Moreover, otoferlin interacts with 32 calbindin-D28k in stimulated IHCs, which was precluded when PKC was inhibited. Similarly, the 33 activity-dependent increase in otoferlin-myosin VI interaction depends on PKC activation. We 34 propose that upon strong hair cell depolarization, PKC phosphorylates otoferlin, thereby enabling it 35 to interact with calbindin-D28k and myosin VI, building a Ca 2+ -dependent signaling complex that 36 possibly regulates different modes of endocytosis. 37 38 Keywords 39 calcium / inner ear / phosphorylation / ribbon synapse / synaptic transmission / 40 41 domain protein otoferlin seems to replace some of these proteins and is currently hypothesized to act 55 as the Ca 2+ sensor for exocytosis in mature IHCs (Roux et al, 2006; Michalski et al, 2017). Different 56 OTOF mutations lead to almost entirely abolished IHC exocytosis and thus to profound deafness in 57 humans and animal models (Yasunaga et al, 1999(Yasunaga et al, , 2000 Roux et al, 2006;Longo-Guess et al, 2007; 58 Marlin et al, 2010; Pangršič et al, 2010; Reisinger et al, 2011). Otoferlin is involved in vesicle priming 59 and fusion, vesicle replenishment, vesicle reformation from bulk endosomes, active zone clearance, 60 and clathrin-mediated endocytosis (Pangršič et al, 2010;Duncker et al, 2013;Jung et al, 2015; Strenzke 61 et al, 2016). It has been reported to interact with several proteins involved in the SV cycle, e.g. Rab8b, 62 myosin VI, CaV1.3 calcium channels, the adaptor protein 2 (AP-2) and endophilin A (Roux et al

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Synaptojanin and Endophilin Mediate Neck Formation during Ultrafast Endocytosis

Cited by 99 publications

References 72 publications

Role of the endolysosomal system in Parkinson’s disease

Role of the endolysosomal system in Parkinson’s disease

Time course and temperature dependence of synaptic vesicle endocytosis

PKCα-dependent interaction of otoferlin and calbindin: evidence for regulation of endocytosis in inner hair cells

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