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Intracellular hyaluronan: Importance for cellular functions.

Spyros S Skandalis1, Theodoros Karalis1, Paraskevi Heldin2

  • 1Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece.

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Hyaluronan, found in extracellular matrices and inside cells, plays roles in cell growth and migration. Intracellular hyaluronan, though not fully understood, impacts cell cycle, motility, and RNA processes.

Keywords:
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Area of Science:

  • Extracellular Matrix Biology
  • Molecular Cell Biology
  • Biochemistry

Background:

  • Hyaluronan (HA)-rich matrices are crucial components of the extracellular matrix (ECM).
  • HA is synthesized by hyaluronan synthases (HAS1, HAS2, HAS3), with complex gene regulation including alternative splicing and non-coding RNAs.
  • HA biosynthesis is upregulated during inflammation and cancer, influenced by cytokines and growth factors.

Purpose of the Study:

  • To explore the presence and potential roles of both extracellular and intracellular hyaluronan.
  • To investigate the binding interactions of hyaluronan with key cellular proteins.
  • To highlight the emerging understanding of intracellular hyaluronan's regulatory functions.

Main Methods:

  • Review of existing literature on hyaluronan synthesis, localization, and binding proteins.
  • Analysis of data regarding the detection of hyaluronan in cytoplasmic and nuclear compartments.
  • Synthesis of evidence linking intracellular hyaluronan to cellular processes.

Main Results:

  • Hyaluronan is detected not only in ECM but also within the cytoplasm and nucleus.
  • Extracellular and intracellular hyaluronan interact with binding proteins like CD44, RHAMM, CDC37, and USP17.
  • Evidence suggests intracellular hyaluronan influences cell cycle, motility, RNA translation/splicing, and autophagy.

Conclusions:

  • Hyaluronan's biological significance extends beyond the extracellular space into intracellular compartments.
  • The precise mechanisms of intracellular hyaluronan localization and function require further elucidation.
  • Intracellular hyaluronan emerges as a key regulator in fundamental cellular activities.