Ca2+ Dependence of Synaptic Vesicle Endocytosis

Jeremy Leitz, Ege T. Kavalali

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Ca2+-dependent synaptic vesicle recycling is essential for structural homeostasis of synapses and maintenance of neurotransmission. Although, the executive role of intrasynaptic Ca2+ transients in synaptic vesicle exocytosis is well established, identifying the exact role of Ca2+ in endocytosis has been difficult. In some studies, Ca2+ has been suggested as an essential trigger required to initiate synaptic vesicle retrieval, whereas others manipulating synaptic Ca2+ concentrations reported a modulatory role for Ca2+ leading to inhibition or acceleration of endocytosis. Molecular studies of synaptic vesicle endocytosis, on the other hand, have consistently focused on the roles of Ca2+-calmodulin dependent phosphatase calcineurin and synaptic vesicle protein synaptotagmin as potential Ca2+ sensors for endocytosis. Most studies probing the role of Ca2+ in endocytosis have relied on measurements of synaptic vesicle retrieval after strong stimulation. Strong stimulation paradigms elicit fusion and retrieval of multiple synaptic vesicles and therefore can be affected by several factors besides the kinetics and duration of Ca2+ signals that include the number of exocytosed vesicles and accumulation of released neurotransmitters thus altering fusion and retrieval processes indirectly via retrograde signaling. Studies monitoring single synaptic vesicle endocytosis may help resolve this conundrum as in these settings the impact of Ca2+ on synaptic fusion probability can be uncoupled from its putative role on synaptic vesicle retrieval. Future experiments using these single vesicle approaches will help dissect the specific role(s) of Ca2+ and its sensors in synaptic vesicle endocytosis.

Original languageEnglish (US)
Pages (from-to)464-476
Number of pages13
JournalNeuroscientist
Volume22
Issue number5
DOIs
StatePublished - Oct 1 2016

Fingerprint

Synaptic Vesicles
Endocytosis
Synaptotagmins
Exocytosis
Calmodulin
Synaptic Transmission
Synapses
Neurotransmitter Agents
Homeostasis
Maintenance

Keywords

  • calcium signaling
  • endocytosis
  • FM1-43
  • synaptic transmission
  • synaptic vesicle recycling
  • SynaptopHluorin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Ca2+ Dependence of Synaptic Vesicle Endocytosis. / Leitz, Jeremy; Kavalali, Ege T.

In: Neuroscientist, Vol. 22, No. 5, 01.10.2016, p. 464-476.

Research output: Contribution to journalReview article

Leitz, Jeremy ; Kavalali, Ege T. / Ca2+ Dependence of Synaptic Vesicle Endocytosis. In: Neuroscientist. 2016 ; Vol. 22, No. 5. pp. 464-476.
@article{051cbe3bc77f4ddd8a1166da780ee1a1,
title = "Ca2+ Dependence of Synaptic Vesicle Endocytosis",
abstract = "Ca2+-dependent synaptic vesicle recycling is essential for structural homeostasis of synapses and maintenance of neurotransmission. Although, the executive role of intrasynaptic Ca2+ transients in synaptic vesicle exocytosis is well established, identifying the exact role of Ca2+ in endocytosis has been difficult. In some studies, Ca2+ has been suggested as an essential trigger required to initiate synaptic vesicle retrieval, whereas others manipulating synaptic Ca2+ concentrations reported a modulatory role for Ca2+ leading to inhibition or acceleration of endocytosis. Molecular studies of synaptic vesicle endocytosis, on the other hand, have consistently focused on the roles of Ca2+-calmodulin dependent phosphatase calcineurin and synaptic vesicle protein synaptotagmin as potential Ca2+ sensors for endocytosis. Most studies probing the role of Ca2+ in endocytosis have relied on measurements of synaptic vesicle retrieval after strong stimulation. Strong stimulation paradigms elicit fusion and retrieval of multiple synaptic vesicles and therefore can be affected by several factors besides the kinetics and duration of Ca2+ signals that include the number of exocytosed vesicles and accumulation of released neurotransmitters thus altering fusion and retrieval processes indirectly via retrograde signaling. Studies monitoring single synaptic vesicle endocytosis may help resolve this conundrum as in these settings the impact of Ca2+ on synaptic fusion probability can be uncoupled from its putative role on synaptic vesicle retrieval. Future experiments using these single vesicle approaches will help dissect the specific role(s) of Ca2+ and its sensors in synaptic vesicle endocytosis.",
keywords = "calcium signaling, endocytosis, FM1-43, synaptic transmission, synaptic vesicle recycling, SynaptopHluorin",
author = "Jeremy Leitz and Kavalali, {Ege T.}",
year = "2016",
month = "10",
day = "1",
doi = "10.1177/1073858415588265",
language = "English (US)",
volume = "22",
pages = "464--476",
journal = "Neuroscientist",
issn = "1073-8584",
publisher = "SAGE Publications Inc.",
number = "5",

}

TY - JOUR

T1 - Ca2+ Dependence of Synaptic Vesicle Endocytosis

AU - Leitz, Jeremy

AU - Kavalali, Ege T.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Ca2+-dependent synaptic vesicle recycling is essential for structural homeostasis of synapses and maintenance of neurotransmission. Although, the executive role of intrasynaptic Ca2+ transients in synaptic vesicle exocytosis is well established, identifying the exact role of Ca2+ in endocytosis has been difficult. In some studies, Ca2+ has been suggested as an essential trigger required to initiate synaptic vesicle retrieval, whereas others manipulating synaptic Ca2+ concentrations reported a modulatory role for Ca2+ leading to inhibition or acceleration of endocytosis. Molecular studies of synaptic vesicle endocytosis, on the other hand, have consistently focused on the roles of Ca2+-calmodulin dependent phosphatase calcineurin and synaptic vesicle protein synaptotagmin as potential Ca2+ sensors for endocytosis. Most studies probing the role of Ca2+ in endocytosis have relied on measurements of synaptic vesicle retrieval after strong stimulation. Strong stimulation paradigms elicit fusion and retrieval of multiple synaptic vesicles and therefore can be affected by several factors besides the kinetics and duration of Ca2+ signals that include the number of exocytosed vesicles and accumulation of released neurotransmitters thus altering fusion and retrieval processes indirectly via retrograde signaling. Studies monitoring single synaptic vesicle endocytosis may help resolve this conundrum as in these settings the impact of Ca2+ on synaptic fusion probability can be uncoupled from its putative role on synaptic vesicle retrieval. Future experiments using these single vesicle approaches will help dissect the specific role(s) of Ca2+ and its sensors in synaptic vesicle endocytosis.

AB - Ca2+-dependent synaptic vesicle recycling is essential for structural homeostasis of synapses and maintenance of neurotransmission. Although, the executive role of intrasynaptic Ca2+ transients in synaptic vesicle exocytosis is well established, identifying the exact role of Ca2+ in endocytosis has been difficult. In some studies, Ca2+ has been suggested as an essential trigger required to initiate synaptic vesicle retrieval, whereas others manipulating synaptic Ca2+ concentrations reported a modulatory role for Ca2+ leading to inhibition or acceleration of endocytosis. Molecular studies of synaptic vesicle endocytosis, on the other hand, have consistently focused on the roles of Ca2+-calmodulin dependent phosphatase calcineurin and synaptic vesicle protein synaptotagmin as potential Ca2+ sensors for endocytosis. Most studies probing the role of Ca2+ in endocytosis have relied on measurements of synaptic vesicle retrieval after strong stimulation. Strong stimulation paradigms elicit fusion and retrieval of multiple synaptic vesicles and therefore can be affected by several factors besides the kinetics and duration of Ca2+ signals that include the number of exocytosed vesicles and accumulation of released neurotransmitters thus altering fusion and retrieval processes indirectly via retrograde signaling. Studies monitoring single synaptic vesicle endocytosis may help resolve this conundrum as in these settings the impact of Ca2+ on synaptic fusion probability can be uncoupled from its putative role on synaptic vesicle retrieval. Future experiments using these single vesicle approaches will help dissect the specific role(s) of Ca2+ and its sensors in synaptic vesicle endocytosis.

KW - calcium signaling

KW - endocytosis

KW - FM1-43

KW - synaptic transmission

KW - synaptic vesicle recycling

KW - SynaptopHluorin

UR - http://www.scopus.com/inward/record.url?scp=84987638626&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84987638626&partnerID=8YFLogxK

U2 - 10.1177/1073858415588265

DO - 10.1177/1073858415588265

M3 - Review article

C2 - 25998187

AN - SCOPUS:84987638626

VL - 22

SP - 464

EP - 476

JO - Neuroscientist

JF - Neuroscientist

SN - 1073-8584

IS - 5

ER -