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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.
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The Lysosome and Intracellular Signalling.

Geoffrey G Hesketh1, Lena Wartosch2, Luther J Davis2

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Lysosomes are key signaling hubs that regulate cell growth and nutrient responses via mTORC1 and transcription factor EB (TFEB). They also store and release calcium, influencing cellular processes.

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Area of Science:

  • Cell Biology
  • Molecular Signaling

Background:

  • Lysosomes serve as the final destination for cellular degradation via endocytosis and autophagy.
  • Lysosomes are critical signaling hubs that integrate nutrient and growth factor signals.
  • The mammalian target of rapamycin complex 1 (mTORC1) pathway is activated on the lysosomal surface.

Purpose of the Study:

  • To elucidate the multifaceted signaling roles of lysosomes beyond their degradative functions.
  • To explore the regulation of transcription factor EB (TFEB) by mTORC1 and its impact on lysosome biogenesis.
  • To investigate the involvement of lysosomes in intracellular calcium (Ca2+) storage and signaling.

Main Methods:

  • Review of current literature on lysosome signaling pathways.
  • Analysis of the mTORC1-TFEB axis in relation to lysosome biogenesis.
  • Discussion of lysosomal calcium release and its interaction with endoplasmic reticulum (ER) calcium stores.

Main Results:

  • Lysosomes regulate cell growth and lysosome biogenesis through the mTORC1-TFEB pathway.
  • TFEB dephosphorylation under starvation promotes nuclear translocation and master regulation of lysosome biogenesis.
  • Lysosomes function as intracellular Ca2+ stores, influencing cellular signaling and membrane fusion.

Conclusions:

  • Lysosomes are dynamic signaling organelles with crucial roles in nutrient sensing, cell growth, and calcium homeostasis.
  • The interplay between lysosomal and ER calcium stores shapes intracellular Ca2+ signaling.
  • Further research is needed to understand how lysosome dynamics and localization affect signaling outcomes.