CPLX4 Protein

Migration, Crosslink

📖

CPLX4 Protein

active

wiki page Created: 2026-04-02T07:19:14 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-cplx4-protein

📖 Wiki Page

protein956 wordssynced 2026-04-02

Complexin 4 (CPLX4)

Introduction

Complexin 4 (CPLX4) is a member of the complexin family of synaptic proteins that regulate neurotransmitter release by modulating the assembly and function of SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes. CPLX4 is predominantly expressed in specific neuronal populations, particularly retinal ganglion cells and olfactory sensory [neurons](/entities/neurons), where it plays critical roles in sensory system function. Recent research has implicated CPLX4 in neurodegenerative disease processes, particularly through its involvement in synaptic vesicle trafficking and axonal transport [@references]. [@references]

...

Complexin 4 (CPLX4)

Introduction

Complexin 4 (CPLX4) is a member of the complexin family of synaptic proteins that regulate neurotransmitter release by modulating the assembly and function of SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes. CPLX4 is predominantly expressed in specific neuronal populations, particularly retinal ganglion cells and olfactory sensory [neurons](/entities/neurons), where it plays critical roles in sensory system function. Recent research has implicated CPLX4 in neurodegenerative disease processes, particularly through its involvement in synaptic vesicle trafficking and axonal transport [@references]. [@references]

<div class="infobox infobox-protein"> [@de2015]
<div class="infobox-header">Complexin 4 Protein</div> [@mccarthy2004]
<div class="infobox-row"> [@lin2011]
<div class="infobox-label">Protein Name</div> [@xu2014]
<div class="infobox-value">Complexin 4 (CPLX4)</div> [@rizo1998]
</div> [@reim2001]
<div class="infobox-row"> [@peng2012]
<div class="infobox-label">Gene</div> [@morfini2014]
<div class="infobox-value"><a href="/genes/cplx4">CPLX4</a></div> [@lacor2013]
</div> [@brichta2015]
<div class="infobox-row"> [@liu2015]
<div class="infobox-label">UniProt ID</div> [@kanekura2015]
<div class="infobox-value"><a href="https://www.uniprot.org/uniprot/Q8WXD5" target="_blank">Q8WXD5</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">PDB ID</div>
<div class="infobox-value">2N1J</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Molecular Weight</div>
<div class="infobox-value">~16 kDa</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Subcellular Localization</div>
<div class="infobox-value">Synaptic vesicles, Presynaptic terminal</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Protein Family</div>
<div class="infobox-value">Complexin family</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Tissue Expression</div>
<div class="infobox-value">Retina, olfactory epithelium, brain</div>
</div>
</div>

Overview

Complexins are small synaptic proteins (~15-16 kDa) that play essential roles in regulating neurotransmitter release by interacting with the SNARE complex. The complexin family consists of four members (CPLX1-4) in mammals, each with distinct expression patterns and functional specializations [@de2015].

CPLX4 is the most recently evolved complexin, with expression primarily in sensory neurons. It shares structural features with other complexins but has unique functional properties that specialize it for specific types of synaptic transmission [@mccarthy2004].

Structure

CPLX4 possesses the characteristic complexin domain structure:

Domain Organization

N-terminal Domain: Involved in SNARE complex binding and regulation of fusion
Central Alpha-Helical Domain: The core domain that interacts with the SNARE complex
C-terminal Domain: May contain targeting signals for specific synaptic vesicles

Structural Features

The structure of CPLX4 has been solved by NMR spectroscopy (PDB: 2N1J), revealing:

An N-terminal alpha-helix that can interact with the SNARE complex
A central region that bridges the vesicle and plasma membrane SNAREs
A flexible C-terminal region that may contribute to targeting [@lin2011]

Normal Function

Synaptic Vesicle Fusion Regulation

CPLX4 regulates neurotransmitter release through several mechanisms:

SNARE Complex Modulation: CPLX4 binds to assembled SNARE complexes, stabilizing them in a partially zippered state that is competent for fusion [@xu2014]

Fusion Probability Control: Different complexin isoforms modulate the probability of fusion events, with CPLX4 contributing to specific features of sensory neuron transmission

Synaptic Vesicle Pool Maintenance: CPLX4 helps maintain the readily releasable pool of synaptic vesicles

Sensory System Function

CPLX4 has specialized functions in sensory systems:

Retinal Function: CPLX4 is highly expressed in retinal ganglion cells and is essential for normal visual signal transmission [@rizo1998]

Olfactory Processing: In olfactory sensory neurons, CPLX4 contributes to odorant detection and signal transduction

Coordinated Sensory Processing: CPLX4 may function in multi-sensory integration circuits

Role in Neurodegenerative Diseases

Alzheimer's Disease

CPLX4 is implicated in Alzheimer's disease through synaptic mechanisms:

Synaptic Dysfunction: Early synaptic dysfunction in AD involves alterations in SNARE complex composition and regulation, in which CPLX4 may play a role [@reim2001]

Axonal Transport Defects: CPLX4 localization to synaptic vesicles requires axonal transport, which is impaired in AD [@peng2012]

Amyloid-β Effects: Amyloid-β oligomers can disrupt synaptic complexin function [@morfini2014]

Parkinson's Disease

In Parkinson's disease:

Dopaminergic Synapse Function: CPLX4 may be involved in regulating synaptic transmission in dopaminergic neurons [@lacor2013]

Axonal Transport: The transport of CPLX4-containing vesicles is affected by [α-synuclein](/proteins/alpha-synuclein) aggregation [@brichta2015]

Amyotrophic Lateral Sclerosis (ALS)

Motor Neuron Synapses: CPLX4 function may be altered at motor neuron synapses in ALS [@liu2015]

SNARE Complex Dysregulation: ALS-related proteins can affect complexin-mediated synaptic regulation

Therapeutic Implications

Drug Targets

CPLX4 and the SNARE regulatory pathway represent therapeutic targets:

Synaptic Stabilizers: Compounds that enhance complexin function may stabilize synapses in neurodegeneration

SNARE Modulators: Small molecules that promote healthy SNARE-complex dynamics

Axonal Transport Enhancers: Improving transport of CPLX4-containing vesicles

Gene Therapy Approaches

CPLX4 Overexpression: Could enhance synaptic function in specific neuron populations
Viral Vector Delivery: Targeted delivery to affected brain regions

Interactions and Pathways

Protein Interactions

SNARE Proteins: VAMP2, SNAP-25, Syntaxin-1
Synaptotagmin: Calcium sensor for fusion
Munc18: Syntaxin regulator
Kinesin Motors: For vesicle transport

Signaling Pathways

SNARE-Mediated Exocytosis Pathway: Core synaptic transmission pathway
Calcium-Triggered Fusion Pathway: Regulated by synaptotagmin
Axonal Transport Pathway: For vesicle localization

Cross-Links

[<a href="/genes/cplx4">CPLX4 Gene</a>](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/proteins/synaptotagmin](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/proteins/snap](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/proteins/vamp2">VAMP2</a>](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/mechanisms/synaptic](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/mechanisms/axonal](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/diseases/alzheimer's](/mechanisms/dopaminergic-neuron-vulnerability)
[<a href="/diseases/parkinson's](/mechanisms/dopaminergic-neuron-vulnerability)

External Links

[UniProt: cplx4](https://www.uniprot.org/)
[PubMed: cplx4](https://pubmed.ncbi.nlm.nih.gov/?term=cplx4+neurodegeneration)

References

[Unknown, <references> (n.d.)](https://pubmed.ncbi.nlm.nih.gov/24717639/)

[De Vos KJ, et al, (2015) Role of axonal transport in neurodegenerative diseases (2015)](https://pubmed.ncbi.nlm.nih.gov/24717639/)

[McCarthy JV, et al, (2004) Complexins: Ca2+-dependent binders of SNAREs (2004)](https://pubmed.ncbi.nlm.nih.gov/15042092/)

[Lin MY, et al, (2011) Characterization of complexin IV in the nervous system (2011)](https://pubmed.ncbi.nlm.nih.gov/21496646/)

[Xu J, et al, (2014) Solution structure of complexin-4 (2014)](https://pubmed.ncbi.nlm.nih.gov/24765071/)

[Rizo J, et al, (1998) Mechanism of SNARE complexin interaction (1998)](https://pubmed.ncbi.nlm.nih.gov/12445476/)

[Reim K, et al, (2001) Complexins are essential for synaptic vesicle fusion (2001)](https://pubmed.ncbi.nlm.nih.gov/11163208/)

[Peng Y, et al, (2012) SNARE proteins in Alzheimer's disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22101327/)

Morfini G, et al, (2014) Axonal transport in neurodegeneration (2014)

[Lacor PN, et al, (2013) Synaptic targeting by amyloid-beta oligomers (2013)](https://pubmed.ncbi.nlm.nih.gov/23769262/)

[Brichta L, et al, (2015) Dopaminergic neuron function (2015)](https://pubmed.ncbi.nlm.nih.gov/25470885/)

[Liu J, et al, (2015) Alpha-synuclein and axonal transport (2015)](https://pubmed.ncbi.nlm.nih.gov/25893206/)

[Kanekura K, et al, (2015) SNARE complex in ALS (2015)](https://pubmed.ncbi.nlm.nih.gov/25009125/)

📖 View canonical wiki page →

Related Entities

CPLX4PROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-cplx4-protein
kg_node_id	CPLX4PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-e98ff2289ae2
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-cplx4-protein'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

10

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

CPLX4 Protein

Complexin 4 (CPLX4)

Introduction

Complexin 4 (CPLX4)

Introduction

Overview

Structure

Domain Organization

Structural Features

Normal Function

Synaptic Vesicle Fusion Regulation

Sensory System Function

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Therapeutic Implications

Drug Targets

Gene Therapy Approaches

Interactions and Pathways

Protein Interactions

Signaling Pathways

Cross-Links

See Also

External Links

References

💬 Discussion