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Mechanisms of Membrane Domain Formation00:59

Mechanisms of Membrane Domain Formation

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Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
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Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

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Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.4K
Lipids as Anchors01:32

Lipids as Anchors

5.8K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
5.8K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

5.9K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Related Experiment Video

Updated: Sep 8, 2025

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

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Disordered Ferlin C2A-C2B Linkers Bind Membranes and Encode Small Linear Motifs.

Ethiene Kwok1, Patricia Khuu1, Erin Huang1

  • 1Department of Biochemistry and Biophysics Oregon State University, Corvallis, OR, USA.

Journal of Molecular Biology
|September 6, 2025
PubMed
Summary

Ferlin protein linkers are not passive spacers. They act as signaling platforms, binding membranes and protein partners, crucial for vesicle trafficking and cellular functions.

Keywords:
IDRdisorderedendocytosislinkermembrane

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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

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Characterization of Proteins by Size-Exclusion Chromatography Coupled to Multi-Angle Light Scattering SEC-MALS
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Characterization of Proteins by Size-Exclusion Chromatography Coupled to Multi-Angle Light Scattering SEC-MALS

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Related Experiment Videos

Last Updated: Sep 8, 2025

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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Characterization of Proteins by Size-Exclusion Chromatography Coupled to Multi-Angle Light Scattering SEC-MALS
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Characterization of Proteins by Size-Exclusion Chromatography Coupled to Multi-Angle Light Scattering SEC-MALS

Published on: June 20, 2019

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Ferlins are key vesicle trafficking proteins featuring C2 domains and disordered linkers.
  • The function of ferlin C2 domains as calcium sensors is known, but linker roles are unclear.
  • Investigating the C2A-C2B linker's role beyond passive spacing is essential.

Purpose of the Study:

  • To investigate the functional significance of vertebrate ferlin C2A-C2B linkers.
  • To identify potential membrane-binding motifs and protein-interaction sites within these linkers.
  • To understand the role of alternative splicing in linker function.

Main Methods:

  • Sequence analysis to identify short linear motifs (SLiMs) and membrane-binding regions.
  • Liposome binding assays using recombinant ferlin C2A-C2B constructs.
  • Fluorescence spectroscopy to detect protein-protein interactions.

Main Results:

  • Ferlin linkers contain SLiMs and membrane-binding sequences, notably in otoferlin and dysferlin.
  • The otoferlin C2A-C2B linker significantly mediates membrane binding and is affected by alternative splicing.
  • Dysferlin linker binds liposomes and interacts with SH3/WW domain proteins.

Conclusions:

  • Vertebrate ferlin C2A-C2B linkers function as signaling platforms, recruiting SLiM-binding partners.
  • Specific linker regions act as membrane-binding 'hotspots,' potentially localizing protein complexes.
  • Linker sequences are critical for ferlin function in membrane trafficking and cellular signaling.