Journal of Biochemistry and Cell Biology
Open Access

Keratins; Vimentin; Desmin; Neurofilaments; Mechanical Strength; Post-translational Modifications

Introduction

Intermediate filaments (IFs) represent a diverse and essential component of the cytoskeleton, contributing significantly to the mechanical strength, structural integrity, and dynamic properties of cells [1]. Unlike actin filaments and microtubules, which are universally present in all eukaryotic cells, IFs exhibit considerable diversity in their protein composition, reflecting their specialized functions across different cell types and tissues [2]. IFs are characterized by their intermediate diameter (8-12 nm), hence their name, and they form stable, insoluble networks within the cytoplasm that resist mechanical stress and provide structural support. The proteins comprising IFs are classified into several families based on their tissue distribution and sequence homology, including keratins (epithelial cells), vimentin (mesenchymal cells), desmin (muscle cells), and neurofilaments (neurons). Each IF family exhibits distinct properties tailored to the specific mechanical and structural requirements of their respective cell types.

The assembly and regulation of IFs are tightly controlled processes involving specific assembly factors, chaperones, and post-translational modifications such as phosphorylation and glycosylation [3]. These mechanisms ensure the proper formation and organization of IF networks, which are essential for maintaining cellular shape, supporting organelle positioning, and responding to mechanical cues. Beyond their structural roles, IFs are implicated in various cellular processes, including cell migration, signaling, and apoptosis, highlighting their functional versatility [4-7]. Dysregulation of IF dynamics is associated with a range of human diseases, including skin disorders (epidermolysis bullosa simplex), muscular dystrophies (desmin-related myopathies), and neurodegenerative conditions (Charcot-Marie-Tooth disease). This review aims to provide a comprehensive overview of intermediate filaments, emphasizing their structural characteristics, functional roles, regulatory mechanisms, and implications in health and disease. By elucidating the multifaceted contributions of IFs to cellular physiology, this understanding will advance our knowledge of cytoskeletal dynamics and inform future therapeutic strategies targeting IF-associated pathologies.

Results and Discussion

Intermediate filaments (IFs) comprise a diverse group of fibrous proteins that vary in composition depending on cell type and tissue [8]. The main IF families include keratins (in epithelial cells), vimentin (in mesenchymal cells), desmin (in muscle cells), and neurofilaments (in neurons). Each IF type exhibits unique structural characteristics tailored to their specific roles in providing mechanical support, maintaining cellular integrity, and responding to environmental stresses. IFs contribute significantly to the mechanical strength and structural resilience of cells and tissues. Unlike actin filaments and microtubules, which are involved in dynamic processes such as cell motility and intracellular transport, IFs form stable networks that withstand mechanical stress and maintain cell shape. For example, keratins in epithelial cells provide resistance to mechanical abrasion, while vimentin in mesenchymal cells supports the structural integrity of organs and tissues [9]. The assembly and organization of IFs are tightly regulated processes involving specific assembly factors, chaperones, and post-translational modifications. These mechanisms control IF polymerization, filament bundling, and interactions with other cytoskeletal components. Phosphorylation, glycosylation, and proteolytic cleavage of IF proteins modulate their stability and function in response to cellular signals and stress conditions.

Beyond their structural roles, IFs participate in diverse cellular processes such as cell migration, adhesion, and signaling. IF networks serve as tracks for molecular motors and scaffolds for organizing cellular organelles and complexes. In muscle cells, desmin IFs anchor sarcomeres and facilitate force transmission during contraction, highlighting their critical role in muscle function. In neurons, neurofilaments support axonal growth and maintain axonal caliber, essential for efficient neuronal signaling. Dysregulation of IF dynamics is implicated in a variety of human diseases, underscoring their importance in maintaining tissue homeostasis. Mutations or aberrant expression of IF proteins can lead to diseases known as IF-related disorders, including skin disorders (e.g., epidermolysis bullosa simplex), muscular dystrophies (e.g., desmin-related myopathies), and neurodegenerative disorders (e.g., Charcot-Marie-Tooth disease) [10]. Understanding the molecular mechanisms underlying IF-associated pathologies offers insights into disease pathogenesis and potential therapeutic interventions. Advancing our understanding of IF biology and regulation holds promise for developing targeted therapies for IF-related diseases. Research efforts focused on elucidating IF assembly pathways, identifying disease-causing mutations, and exploring pharmacological interventions to modulate IF dynamics are critical for translating basic research into clinical applications. Therapeutic strategies aimed at restoring IF function or mitigating IF-related pathologies may offer novel approaches to treating a broad spectrum of human diseases. In conclusion, intermediate filaments represent essential components of the cytoskeleton, contributing to cell strength, flexibility, and function across diverse cell types and tissues. By unraveling the complex roles of IFs in cellular physiology and disease, we can pave the way for innovative therapies and enhance our understanding of fundamental aspects of cellular biology.

Conclusion

Intermediate filaments (IFs) are integral components of the cellular cytoskeleton, playing crucial roles in maintaining mechanical strength, structural integrity, and functional versatility across various cell types and tissues. The diversity of IF proteins, including keratins, vimentin, desmin, and neurofilaments, reflects their specialized functions in different cellular contexts, from providing mechanical support to facilitating cellular processes such as migration, signaling, and organelle positioning. IFs contribute to cellular resilience by forming stable networks that resist mechanical stress and maintain cell shape. Their regulation involves intricate processes of assembly, organization, and dynamic turnover, mediated by specific assembly factors, post-translational modifications, and interactions with other cytoskeletal components. This regulatory complexity ensures the precise control of IF function in response to developmental cues, environmental stimuli, and cellular signaling pathways.

The significance of IFs extends beyond their structural roles, as evidenced by their involvement in disease pathogenesis. Mutations or dysregulation of IF proteins underlie a spectrum of human disorders, including skin diseases, muscular dystrophies, and neurodegenerative conditions. Understanding the molecular mechanisms driving IF-related diseases provides insights into disease pathophysiology and identifies potential targets for therapeutic interventions aimed at restoring IF function or modulating IF dynamics. Future research directions will continue to unravel the complexities of IF biology, focusing on elucidating novel regulatory mechanisms, exploring therapeutic strategies, and translating basic discoveries into clinical applications. Advances in imaging techniques, molecular biology, and pharmacology offer promising avenues for developing targeted therapies that address IF-associated diseases and improve patient outcomes. In conclusion, intermediate filaments represent essential building blocks of cell strength, flexibility, and resilience. Their multifaceted roles in cellular physiology and pathology underscore their importance in maintaining tissue homeostasis and offer opportunities for innovative therapeutic interventions in the field of biomedical research and clinical medicine.

Acknowledgement

None

Conflict of Interest

None

References

1. Niemczewski B (2007) Observations of water cavitation intensity under practical ultrasonic cleaning conditions. Ultrason Sonochem 14: 13-18.

Indexed at, Google Scholar, Crossref

2. Niemczewski B (2009) Influence of concentration of substances used in ultrasonic cleaning in alkaline solutions on cavitation intensity. Ultrason Sonochem 16: 402-7.

 Indexed at, Google Scholar, Crossref

3. Sluis LVD, Versluis M, Wu M, Wesselink P (2007) Passive ultrasonic irrigation of the root canal: a review of the literature. Int Endod J 40: 415-426.

Indexed at, Google Scholar, Crossref

4. Carmen JC, Roeder BL, Nelson JL, Ogilvie RLR, Robison RA, et al. (2005) Treatment of biofilm infections on implants with low-frequency ultrasound and antibiotics. Am J Infect Control 33: 78-82.

Indexed at, Google Scholar, Crossref

5. Dhir S (2013) Biofilm and dental implant: the microbial link. J Indian Soc Periodonto l7: 5-11.

Indexed at, Google Scholar, Crossref

6. Qian Z, Stoodley P, Pitt WG (1996) Effect of low-intensity ultrasound upon biofilm structure from confocal scanning laser microscopy observation. Biomaterials 17: 1975-1980.

Indexed at, Google Scholar, Crossref

7. Mayfield LJAH, Salvi GE, Mombelli A, Loup PJ, Heitz F, et al. (2018) Supportive peri-implant therapy following anti-infective surgical peri-implantitis treatment: 5-year survival and success. Clin Oral Implants Res 29: 1-6.

Indexed at, Google Scholar, Crossref

8. Guéhennec LL, Soueidan A, Layrolle P, Amouriq Y (2007) Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater 23: 844-854.

Indexed at, Google Scholar, Crossref

9. Guehennec LL, Goyenvalle E, Heredia MAL, Weiss P, Amouriq Y, et al. (2008) Histomorphometric analysis of the osseointegration of four different implant surfaces in the femoral epiphyses of rabbits. Clin Oral Implants Res 19: 1103-10.

Indexed at, Google Scholar, Crossref

10. Figuero E, Graziani F, Sanz I, Herrera D, Sanz M, et al. (2014) Management of peri-implant mucositis and peri-implantitis. Periodontol 2000 66: 255-73.

Indexed at, Google Scholar, Crossref