Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Pre-fusion motion state determines the heterogeneity of membrane fusion dynamics for large dense-core vesicles

Xue, Renhao ; Zhang, Enming LU and Wang, Yu (2024) In Acta Physiologica
Abstract

Aim: In neuroendocrine cells, large dense-core vesicles (LDCVs) undergo highly regulated pre-fusion processes before releasing hormones via membrane fusion. Significant heterogeneity has been found for LDCV population based on the dynamics of membrane fusion. However, how the pre-fusion status impacts the heterogeneity of LDCVs still remains unclear. Hence, we explored pre-fusion determinants of heterogeneous membrane fusion procedure of LDCV subpopulations. Methods: We assessed the pre-fusion motion of two LDCV subpopulations with distinct membrane fusion dynamics individually, using total internal reflection fluorescence microscopy. These two subpopulations were isolated by blocking Rho GTPase-dependent actin reorganization using... (More)

Aim: In neuroendocrine cells, large dense-core vesicles (LDCVs) undergo highly regulated pre-fusion processes before releasing hormones via membrane fusion. Significant heterogeneity has been found for LDCV population based on the dynamics of membrane fusion. However, how the pre-fusion status impacts the heterogeneity of LDCVs still remains unclear. Hence, we explored pre-fusion determinants of heterogeneous membrane fusion procedure of LDCV subpopulations. Methods: We assessed the pre-fusion motion of two LDCV subpopulations with distinct membrane fusion dynamics individually, using total internal reflection fluorescence microscopy. These two subpopulations were isolated by blocking Rho GTPase-dependent actin reorganization using Clostridium difficile toxin B (ToxB), which selectively targets the fast fusion vesicle pool. Results: We found that the fast fusion subpopulation was in an active motion mode prior to release, termed “active” LDCV pool, while vesicles from the slow fusion subpopulation were also moving but in a significantly more confined status, forming an “inert” pool. The depletion of the active pool by ToxB also eliminated fast fusion vesicles and was not rescued by pre-treatment with phorbol ester. A mild actin reorganization blocker, latrunculin A, that partially disrupted the active pool, only slightly attenuated the fast fusion subpopulation. Conclusion: The pre-fusion motion state of LDCVs also exhibits heterogeneity and dictates the heterogeneous fusion pore dynamics. Rearrangement of F-actin network mediates vesicle pre-fusion motion and subsequently determines the membrane fusion kinetics.

(Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
exocytosis, large dense-core vesicle, membrane fusion, neuroendocrine cell, pre-fusion motion
in
Acta Physiologica
publisher
Wiley-Blackwell
external identifiers
  • scopus:85185482010
  • pmid:38353019
ISSN
1748-1708
DOI
10.1111/apha.14115
language
English
LU publication?
yes
id
721842b9-7a8d-41c5-9ed8-52fbca03993d
date added to LUP
2024-03-19 14:12:43
date last changed
2024-04-30 14:17:57
@article{721842b9-7a8d-41c5-9ed8-52fbca03993d,
  abstract     = {{<p>Aim: In neuroendocrine cells, large dense-core vesicles (LDCVs) undergo highly regulated pre-fusion processes before releasing hormones via membrane fusion. Significant heterogeneity has been found for LDCV population based on the dynamics of membrane fusion. However, how the pre-fusion status impacts the heterogeneity of LDCVs still remains unclear. Hence, we explored pre-fusion determinants of heterogeneous membrane fusion procedure of LDCV subpopulations. Methods: We assessed the pre-fusion motion of two LDCV subpopulations with distinct membrane fusion dynamics individually, using total internal reflection fluorescence microscopy. These two subpopulations were isolated by blocking Rho GTPase-dependent actin reorganization using Clostridium difficile toxin B (ToxB), which selectively targets the fast fusion vesicle pool. Results: We found that the fast fusion subpopulation was in an active motion mode prior to release, termed “active” LDCV pool, while vesicles from the slow fusion subpopulation were also moving but in a significantly more confined status, forming an “inert” pool. The depletion of the active pool by ToxB also eliminated fast fusion vesicles and was not rescued by pre-treatment with phorbol ester. A mild actin reorganization blocker, latrunculin A, that partially disrupted the active pool, only slightly attenuated the fast fusion subpopulation. Conclusion: The pre-fusion motion state of LDCVs also exhibits heterogeneity and dictates the heterogeneous fusion pore dynamics. Rearrangement of F-actin network mediates vesicle pre-fusion motion and subsequently determines the membrane fusion kinetics.</p>}},
  author       = {{Xue, Renhao and Zhang, Enming and Wang, Yu}},
  issn         = {{1748-1708}},
  keywords     = {{exocytosis; large dense-core vesicle; membrane fusion; neuroendocrine cell; pre-fusion motion}},
  language     = {{eng}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Acta Physiologica}},
  title        = {{Pre-fusion motion state determines the heterogeneity of membrane fusion dynamics for large dense-core vesicles}},
  url          = {{http://dx.doi.org/10.1111/apha.14115}},
  doi          = {{10.1111/apha.14115}},
  year         = {{2024}},
}