TSPAN7 - tetraspanin 7 |Elisa - Clia - Antibody - Protein

Background

Tetraspanin 7 (TSPAN7) is a member of the tetraspanin superfamily, a group of membrane proteins involved in various cellular functions such as signaling, adhesion, and intracellular trafficking. Tetraspanins are characterized by their distinctive structure, containing four transmembrane domains. TSPAN7 is primarily expressed in the central nervous system, particularly in neurons, and is also found in certain immune cells. TSPAN7 is of interest due to its involvement in neurological processes and its role in neurodevelopmental disorders, most notably X-linked intellectual disability (XLID). Mutations or dysregulation of TSPAN7 have been implicated in cognitive deficits, autism spectrum disorders, and other neurological conditions, highlighting its importance in normal brain function.

The primary role of TSPAN7 appears to be in facilitating cell-cell interactions and maintaining synaptic function. Through its association with other proteins in the tetraspanin web—an organized network of tetraspanins and their partner proteins—TSPAN7 modulates cellular signaling pathways crucial for neuronal growth, differentiation, and communication. These functions make TSPAN7 essential for neural development and synaptic plasticity, processes that underlie learning and memory.

Protein Structure

The TSPAN7 protein has a typical tetraspanin structure, which includes several key features that allow it to participate in membrane interactions and signaling pathways:

Transmembrane Domains:

• TSPAN7 is characterized by four hydrophobic transmembrane domains (TM1–TM4). These domains anchor the protein within the cell membrane and play a role in the formation of the tetraspanin web, a network of tetraspanin proteins and their associated molecules. The arrangement of these transmembrane segments is critical for TSPAN7's structural stability and for its ability to interact with other membrane proteins.

Extracellular Loops:

• TSPAN7 contains two extracellular loops—a small extracellular loop (SEL) and a large extracellular loop (LEL). The LEL is unique to each tetraspanin and is essential for specific protein-protein interactions. It consists of conserved cysteine residues that form disulfide bonds, stabilizing the structure of the loop and facilitating binding with other proteins.
• The LEL is particularly important for TSPAN7’s interactions with integrins and other cell adhesion molecules. This loop contributes to the specificity of TSPAN7's interactions and its ability to modulate cellular functions related to adhesion and signaling.

Intracellular Regions:

• The protein also has short cytoplasmic N- and C-terminal tails, which play a role in intracellular signaling and may mediate interactions with cytoplasmic proteins. These tails are relatively short but contain motifs that can be phosphorylated, allowing TSPAN7 to be involved in signaling cascades triggered by external signals.

Glycosylation and Post-Translational Modifications:

• TSPAN7 may undergo N-linked glycosylation in its extracellular loop, contributing to its stability and functional interactions. Additionally, TSPAN7 can be phosphorylated, a post-translational modification that can influence its interaction with other proteins and its role in signaling pathways.

The arrangement of these structural features allows TSPAN7 to function effectively as a scaffold within the membrane, forming complexes with other proteins and facilitating signaling processes essential for cell communication and adhesion.

Classification and Subtypes

TSPAN7 belongs to the tetraspanin family, which includes over 30 members in humans. These proteins are highly conserved and are classified based on their structural features, particularly the presence of four transmembrane domains and their large extracellular loop. Tetraspanins do not have further subdivisions within their family; however, individual tetraspanins like TSPAN7 can have specific tissue distributions and functions, distinguishing them functionally from other tetraspanins.

Function and Biological Significance

TSPAN7 is involved in several critical biological functions, especially within the nervous system:

Cell Adhesion and Synaptic Function:

• TSPAN7 modulates cell adhesion, particularly through its interactions with integrins and other adhesion molecules. This role is especially crucial in the context of synaptic stability and plasticity, where TSPAN7 contributes to the maintenance and remodeling of synaptic structures.
• In neurons, TSPAN7 is involved in dendritic spine formation, a process that supports synaptic connections and is essential for learning and memory. By stabilizing these structures, TSPAN7 helps maintain proper synaptic function.

Neuronal Growth and Differentiation:

• TSPAN7 influences neuronal growth and differentiation by acting as a scaffold for various signaling pathways. For instance, it modulates pathways that promote neurite outgrowth, a process critical for neural circuit formation during development.
• The protein also plays a role in axonal guidance and migration, helping neurons establish their connections within the brain.

Role in the Immune System:

• Beyond the nervous system, TSPAN7 has a functional presence in immune cells, where it regulates cell migration and adhesion. This function is particularly relevant in the context of inflammation and immune surveillance.

Involvement in Signaling Pathways:

• TSPAN7 serves as a platform for signal transduction by forming complexes with other membrane receptors. Through these interactions, TSPAN7 participates in signaling pathways that regulate cell survival, proliferation, and differentiation.
• It has been linked to pathways involving integrins, EGFR, and other growth factor receptors, showing its broad impact on cellular signaling.

Clinical Issues

TSPAN7’s involvement in neural development and synaptic function is evident from the neurological conditions associated with its dysfunction. Mutations or deletions in the TSPAN7 gene are associated with a range of neurodevelopmental and neuropsychiatric disorders, most notably X-linked intellectual disability (XLID). Clinical issues associated with TSPAN7 dysfunction include:

X-Linked Intellectual Disability (XLID):

• TSPAN7 mutations are one of the causes of XLID, a disorder characterized by cognitive impairment, learning difficulties, and delayed developmental milestones. XLID is particularly significant because it often includes behavioral features such as impulsivity, hyperactivity, and, in some cases, autism spectrum disorder (ASD)-like symptoms.

Autism Spectrum Disorders (ASD):

• TSPAN7 dysregulation has been linked to autism spectrum disorders, suggesting that it plays a role in the social and cognitive deficits seen in ASD. The involvement of TSPAN7 in synaptic plasticity and neural network formation may underlie these associations.

Epilepsy:

• There is evidence suggesting that alterations in TSPAN7 expression or mutations may contribute to epilepsy, particularly in patients with comorbid intellectual disability. This relationship is likely due to the disruption of synaptic function and neuronal connectivity caused by TSPAN7 dysfunction.

Other Neurological Conditions:

• Some studies have indicated that TSPAN7 might be involved in mood disorders or schizophrenia, though the precise mechanisms are not well understood. As TSPAN7 influences synaptic plasticity and stability, any dysregulation may contribute to broader cognitive or mood-related symptoms.

Role in Cancer:

• Though primarily studied for its role in neurology, recent studies have explored TSPAN7’s role in cancer. Tetraspanins are known to influence cancer cell migration and invasion, and TSPAN7’s interaction with integrins and other molecules may facilitate these processes in certain cancers, making it a potential biomarker or therapeutic target.

Summary

TSPAN7, a member of the tetraspanin family, is a transmembrane protein with a well-defined structure that includes four transmembrane domains, extracellular loops, and short intracellular tails. This structure allows TSPAN7 to participate in cell signaling and adhesion, particularly within the nervous system. TSPAN7 is essential for neural development, where it modulates synaptic stability, dendritic spine formation, and neuronal differentiation. It is also expressed in immune cells, where it plays a role in cell adhesion and migration.

Mutations or dysregulation of TSPAN7 are associated with neurodevelopmental disorders, particularly X-linked intellectual disability (XLID) and autism spectrum disorders. These associations underscore TSPAN7’s importance in cognitive and behavioral function. There is also emerging evidence linking TSPAN7 to epilepsy and potentially to cancer, highlighting its diverse roles across different tissues and disease contexts.