Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon

Summary Bidirectional transport is a key issue in cellular biology. It requires coordination between microtubule-associated molecular motors that work in opposing directions. The major retrograde and anterograde motors involved in bidirectional transport are cytoplasmic dynein and conventional kines...

Full description

Bibliographic Details
Main Authors: Michal Segal, Ilya Soifer, Heike Petzold, Jonathon Howard, Michael Elbaum, Orly Reiner
Format: Article
Language:English
Published: The Company of Biologists 2012-01-01
Series:Biology Open
Subjects:
Online Access:http://bio.biologists.org/content/1/3/220
_version_ 1829530349102694400
author Michal Segal
Ilya Soifer
Heike Petzold
Jonathon Howard
Michael Elbaum
Orly Reiner
author_facet Michal Segal
Ilya Soifer
Heike Petzold
Jonathon Howard
Michael Elbaum
Orly Reiner
author_sort Michal Segal
collection DOAJ
description Summary Bidirectional transport is a key issue in cellular biology. It requires coordination between microtubule-associated molecular motors that work in opposing directions. The major retrograde and anterograde motors involved in bidirectional transport are cytoplasmic dynein and conventional kinesin, respectively. It is clear that failures in molecular motor activity bear severe consequences, especially in the nervous system. Neuronal migration may be impaired during brain development, and impaired molecular motor activity in the adult is one of the hallmarks of neurodegenerative diseases leading to neuronal cell death. The mechanisms that regulate or coordinate kinesin and dynein activity to generate bidirectional transport of the same cargo are of utmost importance. We examined how Ndel1, a cytoplasmic dynein binding protein, may regulate non-vesicular bidirectional transport. Soluble Ndel1 protein, Ndel1-derived peptides or control proteins were mixed with fluorescent beads, injected into the squid giant axon, and the bead movements were recorded using time-lapse microscopy. Automated tracking allowed for extraction and unbiased analysis of a large data set. Beads moved in both directions with a clear bias to the anterograde direction. Velocities were distributed over a broad range and were typically slower than those associated with fast vesicle transport. Ironically, the main effect of Ndel1 and its derived peptides was an enhancement of anterograde motion. We propose that they may function primarily by inhibition of dynein-dependent resistance, which suggests that both dynein and kinesin motors may remain engaged with microtubules during bidirectional transport.
first_indexed 2024-12-16T18:03:06Z
format Article
id doaj.art-194c3f4b27414ef2b8444817cc4e7658
institution Directory Open Access Journal
issn 2046-6390
language English
last_indexed 2024-12-16T18:03:06Z
publishDate 2012-01-01
publisher The Company of Biologists
record_format Article
series Biology Open
spelling doaj.art-194c3f4b27414ef2b8444817cc4e76582022-12-21T22:22:00ZengThe Company of BiologistsBiology Open2046-63902012-01-011322023110.1242/bio.20123072012307Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axonMichal Segal0Ilya Soifer1Heike Petzold2Jonathon Howard3Michael Elbaum4Orly Reiner5 Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany Department of Materials and Interfaces, The Weizmann Institute of Science, Rehovot 76100, Israel Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel Summary Bidirectional transport is a key issue in cellular biology. It requires coordination between microtubule-associated molecular motors that work in opposing directions. The major retrograde and anterograde motors involved in bidirectional transport are cytoplasmic dynein and conventional kinesin, respectively. It is clear that failures in molecular motor activity bear severe consequences, especially in the nervous system. Neuronal migration may be impaired during brain development, and impaired molecular motor activity in the adult is one of the hallmarks of neurodegenerative diseases leading to neuronal cell death. The mechanisms that regulate or coordinate kinesin and dynein activity to generate bidirectional transport of the same cargo are of utmost importance. We examined how Ndel1, a cytoplasmic dynein binding protein, may regulate non-vesicular bidirectional transport. Soluble Ndel1 protein, Ndel1-derived peptides or control proteins were mixed with fluorescent beads, injected into the squid giant axon, and the bead movements were recorded using time-lapse microscopy. Automated tracking allowed for extraction and unbiased analysis of a large data set. Beads moved in both directions with a clear bias to the anterograde direction. Velocities were distributed over a broad range and were typically slower than those associated with fast vesicle transport. Ironically, the main effect of Ndel1 and its derived peptides was an enhancement of anterograde motion. We propose that they may function primarily by inhibition of dynein-dependent resistance, which suggests that both dynein and kinesin motors may remain engaged with microtubules during bidirectional transport.http://bio.biologists.org/content/1/3/220MicrotubulesCytoplasmic dyneinKinesinRetrograde transportAnterograde transport
spellingShingle Michal Segal
Ilya Soifer
Heike Petzold
Jonathon Howard
Michael Elbaum
Orly Reiner
Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
Biology Open
Microtubules
Cytoplasmic dynein
Kinesin
Retrograde transport
Anterograde transport
title Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
title_full Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
title_fullStr Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
title_full_unstemmed Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
title_short Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
title_sort ndel1 derived peptides modulate bidirectional transport of injected beads in the squid giant axon
topic Microtubules
Cytoplasmic dynein
Kinesin
Retrograde transport
Anterograde transport
url http://bio.biologists.org/content/1/3/220
work_keys_str_mv AT michalsegal ndel1derivedpeptidesmodulatebidirectionaltransportofinjectedbeadsinthesquidgiantaxon
AT ilyasoifer ndel1derivedpeptidesmodulatebidirectionaltransportofinjectedbeadsinthesquidgiantaxon
AT heikepetzold ndel1derivedpeptidesmodulatebidirectionaltransportofinjectedbeadsinthesquidgiantaxon
AT jonathonhoward ndel1derivedpeptidesmodulatebidirectionaltransportofinjectedbeadsinthesquidgiantaxon
AT michaelelbaum ndel1derivedpeptidesmodulatebidirectionaltransportofinjectedbeadsinthesquidgiantaxon
AT orlyreiner ndel1derivedpeptidesmodulatebidirectionaltransportofinjectedbeadsinthesquidgiantaxon