Menu

Close

A non-canonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

Saipraveen Srinivasan, Christoph J. Burckhardt, Madhura Bhave, Zhiming Chen, Ping-Hung Chen, Xinxin Wang, Gaudenz Danuser, Sandra L. Schmid

Preprint posted on January 22, 2018 https://www.biorxiv.org/content/early/2018/01/22/251983?%3Fcollection=

The roles of dynamin-1 in neurons are well studied, but what is its function in non-neuronal cells? This preprint investigates the roles of dynamin in regulating early stages of clathrin-mediated endocytosis.

Selected by Penelope La-Borde

Background

The title of this preprint caught my attention, as I am interested in clathrin-mediated endocytosis (CME). In addition to the well-studied roles of dynamin-1 (Dyn1) in membrane fission during the rapid recycling of synaptic vesicles in neurons, dynamin also plays a role in regulating early stages of CME. Little is understood about this regulatory role and the work in this preprint seeks to investigate further.

Key findings

This preprint studies the isoform-specific roles of Dyn1 and dynamin-2 (Dyn2) in regulating early stages of CME, revealing that they have distinct functions. Dyn1 and Dyn2 are shown to be differently recruited to clathrin-coated pits (CCPs). Dyn2 is gradually recruited to CCPs and displays a burst of accumulation when the clathrin-coated vesicle (CCV) is released, whereas Dyn1 recruitment to CCPs is barely detectable. Despite these low levels of Dyn1, the researchers found that activation of Dyn1 increases rates of CCP initiation and maturation. They also identified Sorting nexin 9 (SNX9) as a binding partner of active Dyn1, required for its effect on CCP maturation.

Why is this preprint important?

To show the physiological relevance of their findings, the researchers studied the effect of epidermal growth factor (EGF) on Dyn1. They found that Dyn1 is activated downstream of epidermal growth factor receptors (EGFRs), increasing CCP initiation and maturation rates.

What I like about this preprint

I like the use of genome-edited cells in this work, enabling the authors to study the dynamin isoforms at their endogenous levels. This avoids many of the potential problems involved with overexpression of the protein of interest. This is a very thorough study, using multiple approaches to confirm key findings.

Future directions

Next steps for this work could include identifying more isoform-specific binding partners for dynamin in non-neuronal cells. Whilst SNX9 has been revealed as a binding partner for active Dyn1 that is required for its CCP maturation effects, it would be interesting to discover any binding partners that mediate the effects of Dyn1 on CCP initiation. The functions of SNX9 in CME could be elucidated further; perhaps, even its Dyn-1 binding site could be discovered, allowing mutagenesis of this site for further study.

Another area for future work suggested in the preprint is to investigate whether other signalling receptors can modify the composition of their CCPs to change their maturation rates, possibly involving Dyn1, as it is the case for EGFRs.

Furthermore, to investigate how Dyn1 and Dyn2 achieve their distinct functions in regulating early stages of CME, it would be interesting to discover which specific residues are responsible for these functions. This would then allow mutagenesis studies, potentially switching the functionalities between the isoforms by mutating key residues.

It could also be interesting to study dynamin-3, the third isoform of dynamin in vertebrates, to see whether it has distinct functions to Dyn1 and Dyn2.

 

Posted on: 29th April 2018

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the biochemistry category:

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Atlas of Subcellular RNA Localization Revealed by APEX-seq

    Furqan M Fazal, Shuo Han, Pornchai Kaewsapsak, et al.

    AND

    Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules

    Alejandro Padron, Shintaro Iwasaki, Nicholas Ingolia



    Selected by Christian Bates

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine

    Activation of intracellular transport by relieving KIF1C autoinhibition

    Nida Siddiqui, Alice Bachmann, Alexander J Zwetsloot, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    1

    Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

    Jonathan P Gumucio, Austin H Qasawa, Patrick J Ferrara, et al.



    Selected by Pablo Ranea Robles

    Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex

    Diego Gauto, Leandro Estrozi, Charles Schwieters, et al.



    Selected by Reid Alderson

    1

    Disrupting Transcriptional Feedback Yields an Escape-Resistant Antiviral

    Sonali Chaturvedi, Marie Wolf, Noam Vardi, et al.



    Selected by Pavithran Ravindran

    1

    Structure of a cytochrome-based bacterial nanowire

    David J Filman, Stephen F Marino, Joy E Ward, et al.



    Selected by Amberley Stephens

    Multi-color single molecule imaging uncovers extensive heterogeneity in mRNA decoding

    Sanne Boersma, Deepak Khuperkar, Bram M.P. Verhagen, et al.

    AND

    Live-cell single RNA imaging reveals bursts of translational frameshifting

    Kenneth R Lyon Jr, Luis U Aguilera, Tatsuya Morisaki, et al.



    Selected by Nicola Stevenson

    Retrieving High-Resolution Information from Disordered 2D Crystals by Single Particle Cryo-EM

    Ricardo Righetto, Nikhil Biyani, Julia Kowal, et al.



    Selected by David Wright

    Structural venomics: evolution of a complex chemical arsenal by massive duplication and neofunctionalization of a single ancestral fold

    Sandy Steffany Pineda, Yanni K-Y Chin, Eivind A.B. Undheim, et al.



    Selected by Tessa Sinnige

    Microtubules Gate Tau Condensation to Spatially Regulate Microtubule Functions

    Ruensern Tan, Aileen J. Lam, Tracy Tan, et al.

    AND

    Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

    Valerie Siahaan, Jochen Krattenmacher, Amayra Hernandez-Vega, et al.



    Selected by Satish Bodakuntla

    2

    The structural basis for release factor activation during translation termination revealed by time-resolved cryogenic electron microscopy

    Ziao Fu, Gabriele Indrisiunaite, Sandip Kaledhonkar, et al.



    Selected by David Wright

    The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis.

    Joseph Franics McKenna, Daniel Rolfe, Stephen E D Webb, et al.



    Selected by Marc Somssich

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    Refolding activity of bacterial Hsp90 in vivo reveals ancient chaperoning function

    Tania Moran Luengo, Toveann Ahlnas, Anna T. Hoekstra, et al.



    Selected by Tessa Sinnige

    Also in the cell biology category:

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    1

    Actomyosin-II facilitates long-range retrograde transport of large cargoes by controlling axonal radial contractility

    Tong Wang, Wei Li, Sally Martin, et al.



    Selected by Ivana Viktorinov√°

    Atlas of Subcellular RNA Localization Revealed by APEX-seq

    Furqan M Fazal, Shuo Han, Pornchai Kaewsapsak, et al.

    AND

    Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules

    Alejandro Padron, Shintaro Iwasaki, Nicholas Ingolia



    Selected by Christian Bates

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine

    Stable knockout and complementation of receptor expression using in vitro cell line derived reticulocytes for dissection of host malaria invasion requirements

    Timothy J Satchwell, Katherine E Wright, Katy L Haydn-Smith, et al.



    Selected by Alyson Smith

    Maintenance of spatial gene expression by Polycomb-mediated repression after formation of a vertebrate body plan

    Julien Rougot, Naomi D Chrispijn, Marco Aben, et al.



    Selected by Yen-Chung Chen

    1

    Activation of intracellular transport by relieving KIF1C autoinhibition

    Nida Siddiqui, Alice Bachmann, Alexander J Zwetsloot, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    1

    A non-canonical arm of UPRER mediates longevity through ER remodeling and lipophagy.

    Joseph R Daniele, Ryo Higuchi-Sanabria, Vidhya Ramachandran, et al.



    Selected by Sandra Franco Iborra

    1

    Basal extrusion drives cell invasion and mechanical stripping of E-cadherin

    John Fadul, Gloria M Slattum, Nadja M Redd, et al.



    Selected by William Hill

    Ribosomal DNA and the rDNA-binding protein Indra mediate non-random sister chromatid segregation in Drosophila male germline stem cells

    George Watase, Yukiko Yamashita



    Selected by Maiko Kitaoka

    An F-actin shell ruptures the nuclear envelope by sorting pore-dense and pore-free membranes in meiosis of starfish oocytes

    Natalia Wesolowska, Pedro Machado, Celina Geiss, et al.



    Selected by Maiko Kitaoka

    1

    Multi-color single molecule imaging uncovers extensive heterogeneity in mRNA decoding

    Sanne Boersma, Deepak Khuperkar, Bram M.P. Verhagen, et al.



    Selected by Lorenzo Lafranchi

    Multi-color single molecule imaging uncovers extensive heterogeneity in mRNA decoding

    Sanne Boersma, Deepak Khuperkar, Bram M.P. Verhagen, et al.

    AND

    Live-cell single RNA imaging reveals bursts of translational frameshifting

    Kenneth R Lyon Jr, Luis U Aguilera, Tatsuya Morisaki, et al.



    Selected by Nicola Stevenson

    A non-canonical arm of UPRER mediates longevity through ER remodeling and lipophagy.

    Joseph R Daniele, Ryo Higuchi-Sanabria, Vidhya Ramachandran, et al.



    Selected by Sandra Malmgren Hill

    Microtubules Gate Tau Condensation to Spatially Regulate Microtubule Functions

    Ruensern Tan, Aileen J. Lam, Tracy Tan, et al.

    AND

    Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

    Valerie Siahaan, Jochen Krattenmacher, Amayra Hernandez-Vega, et al.



    Selected by Satish Bodakuntla

    2

    Also in the molecular biology category:

    MRE11-RAD50-NBS1 activates Fanconi Anemia R-loop suppression at transcription-replication conflicts

    Emily Yun-Chia Chang, James P Wells, Shu-Huei Tsai, et al.



    Selected by Katie Weiner

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Atlas of Subcellular RNA Localization Revealed by APEX-seq

    Furqan M Fazal, Shuo Han, Pornchai Kaewsapsak, et al.

    AND

    Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules

    Alejandro Padron, Shintaro Iwasaki, Nicholas Ingolia



    Selected by Christian Bates

    Unlimited genetic switches for cell-type specific manipulation

    Jorge Garcia-Marques, Ching-Po Yang, Isabel Espinosa-Medina, et al.



    Selected by Rafael Almeida

    1

    Stable knockout and complementation of receptor expression using in vitro cell line derived reticulocytes for dissection of host malaria invasion requirements

    Timothy J Satchwell, Katherine E Wright, Katy L Haydn-Smith, et al.



    Selected by Alyson Smith

    The coordination of terminal differentiation and cell cycle exit is mediated through the regulation of chromatin accessibility

    Yiqin Ma, Daniel J McKay, Laura Buttitta



    Selected by Gabriel Aughey

    1

    Disrupting Transcriptional Feedback Yields an Escape-Resistant Antiviral

    Sonali Chaturvedi, Marie Wolf, Noam Vardi, et al.



    Selected by Pavithran Ravindran

    1

    Multi-color single molecule imaging uncovers extensive heterogeneity in mRNA decoding

    Sanne Boersma, Deepak Khuperkar, Bram M.P. Verhagen, et al.



    Selected by Lorenzo Lafranchi

    Multi-color single molecule imaging uncovers extensive heterogeneity in mRNA decoding

    Sanne Boersma, Deepak Khuperkar, Bram M.P. Verhagen, et al.

    AND

    Live-cell single RNA imaging reveals bursts of translational frameshifting

    Kenneth R Lyon Jr, Luis U Aguilera, Tatsuya Morisaki, et al.



    Selected by Nicola Stevenson

    A non-canonical arm of UPRER mediates longevity through ER remodeling and lipophagy.

    Joseph R Daniele, Ryo Higuchi-Sanabria, Vidhya Ramachandran, et al.



    Selected by Sandra Malmgren Hill

    Retrieving High-Resolution Information from Disordered 2D Crystals by Single Particle Cryo-EM

    Ricardo Righetto, Nikhil Biyani, Julia Kowal, et al.



    Selected by David Wright

    The modular mechanism of chromocenter formation in Drosophila

    Madhav Jagannathan, Ryan Cummings, Yukiko M Yamashita



    Selected by Maiko Kitaoka

    1

    The structural basis for release factor activation during translation termination revealed by time-resolved cryogenic electron microscopy

    Ziao Fu, Gabriele Indrisiunaite, Sandip Kaledhonkar, et al.



    Selected by David Wright

    The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis.

    Joseph Franics McKenna, Daniel Rolfe, Stephen E D Webb, et al.



    Selected by Marc Somssich

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction

    Joshua A. Weinstein, Aviv Regev, Feng Zhang



    Selected by Theo Sanderson

    2

    Close