Presynaptic Precursor Vesicles—Cargo, Biogenesis, and Kinesin-Based Transport across Species

Petzoldt, Astrid G.

doi:10.3390/cells12182248

Cited by 7 publications

(3 citation statements)

References 166 publications

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“…Ca V 1.3 channel localization can impact presynaptic calcium responses as well as both spontaneous and evoked vesicle fusion ( Brandt et al, 2005 ; Trapani & Nicolson, 2011 ). In addition, calcium channels have been shown to be transported in synaptic precursor vesicles ( Petzoldt, 2023 ). We used immunohistochemistry to examine Ca V 1.3 clusters and Rib b to label ribbons ( Figure 6A - B ).…”

Section: Resultsmentioning

confidence: 99%

“…After budding from the trans-Golgi, these precursors are carried to presynaptic terminals along axonal microtubules via kinesin motors and mature into synaptic vesicles at the presynapse ( Santos et al, 2009 ; Rizzoli, 2014 ). Precursor vesicles can contain many presynaptic components including: Rab3a, CSP, Vglut, Piccolo, Bassoon, SNARE proteins, Neurexins and calcium channels (reviewed in: ( Petzoldt, 2023 )). In our kif1aa mutants we show that several of these cargos such as Rab3a, CSP, and Vglut3 fail to localize properly at the presynaptic AZ in hair cells ( Figures 3 , Figure 3-S1 ).…”

Section: Discussionmentioning

confidence: 99%

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Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells

David,

Pinter,

Nguyen

et al. 2024

Preprint

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Sensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This sensory transmission necessitates rapid and sustained neurotransmitter release, which relies on a large pool of synaptic vesicles at the hair-cell presynapse. Work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, but how new synaptic material reaches the presynapse in hair cells is not known. We show that the kinesin motor protein Kif1a and an intact microtubule network are necessary to enrich synaptic vesicles at the presynapse in hair cells. We use genetics and pharmacology to disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. We find that these manipulations decrease synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, along with in vivo calcium imaging and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function. Kif1a mutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Additionally, we find that kif1a mutants exhibit impaired rheotaxis, a behavior reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-based microtubule transport is critical to enrich synaptic vesicles at the active zone in hair cells, a process that is vital for proper ribbon-synapse function.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells

David,

Pinter,

Nguyen

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…RABs are involved in membrane trafficking and vesicle fusion/fission by interacting with numerous proteins including its effector which interacts with the active form of RABs [ 40 , 41 ]. Indeed, GARIN1B and GARIN3 possess a RAB2-binding domain in the N-terminus and bind to RAB2A/B, however, in the WB study, we show that GARIN3 interacts with both the CA and CN forms of RAB2A/B in HEK293T cells ( Fig 7A and 7B ), and GARIN3 is present in mature spermatozoa ( Fig 6B ).…”

Section: Discussionmentioning

confidence: 99%

Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads

Wang,

Iida-Norita,

Mashiko

et al. 2024

PLoS Genet

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Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.

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Tumor microtubes: A new potential therapeutic target for high-grade gliomas

Guo,

Li,

et al. 2024

Journal of Neuropathology &Amp; Experimental Neurology

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High-grade infiltrating gliomas are highly aggressive and fatal brain tumors that present significant challenges for research and treatment due to their complex microenvironment and tissue structure. Recent discovery of tumor microtubes (TMs) has provided new insights into how high-grade gliomas develop in the brain and resist treatment. TMs are unique, ultra-long, and highly functional membrane protrusions that form multicellular networks and play crucial roles in glioma invasiveness, drug resistance, recurrence, and heterogeneity. This review focuses on the different roles that TMs play in glioma cell communication, material transport, and tumor cell behavior. Specifically, non-connecting TMs primarily promote glioma invasiveness, likely related to their role in enhancing cell motility. On the other hand, interconnecting TMs form functional and communication networks by connecting with surrounding astrocytes and neurons, thereby promoting glioma malignancy. We summarize the factors that influence the formation of TMs in gliomas and current strategies targeting TMs. As the understanding of TMs advances, we are closer to uncovering whether they might be the long-sought Achilles’ heel of treatment-resistant gliomas. By delving deeper into TMs research, we hope to develop more effective therapeutic strategies for patients with malignant gliomas.

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Presynaptic Precursor Vesicles—Cargo, Biogenesis, and Kinesin-Based Transport across Species

Cited by 7 publications

References 166 publications

Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells

Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells

Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads

Tumor microtubes: A new potential therapeutic target for high-grade gliomas

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