A kiss-and-run mechanism, to be more specific a novel form of endocytic recycling in cells that brings previously top dog signaling receptors back to their site of action with fantastic rapidity when a cell wants to pay around again.
Clathrin-Associated Recycling Pathway
cells by which it is taken in (endocytosis) and then removed from the cell by means of recycling. The ‘fast’ tubulovesicular (TV) and slow TV recycling pathways are known, but here the researchers reveal a new recycling mechanism that works via a special ‘kiss-and-run’ membrane fusion process.
This is the first full recycling event that recycles cargo quickly and in bulk, but it does so using a novel set of molecular machinery to generate specialized recycling carriers resulting in this novel membrane fusion event (hence its designation as the clathrin associated fast endosomal recycling pathway or CARP). The researchers used state-of-the-art imaging techniques to track the transient fusion of these clathrin/AP1-associated recycling carriers at the plasma membrane, followed by their retrieval and release back into the cell.
‘Perhaps the most interesting aspect of our work is that some of these clathrin/AP1-associated recycling carriers can actually start a transient process of fusion with the plasma membrane, which they then abandon before fusing completely,’ said lead investigator Dr. He Kangmin, from NUSIBR. The cell-signaling receptor GPCR β2 adrenergic and the growth factor receptor EGF-R can be quickly recycled back to the cell surface through this unusual kiss-and-run process.
Why This Is Big Deal
Discovery of this new endocytic recycling pathway will thus provide an innovative insight into understanding cellular signaling and regulation. By offering an alternative faster recycling route for important cell-ranking receptors, the CARP pathway might help boost the efficiency by which the cell is able to adjust its responses to rapidly changing conditions in the extracellular environment.
For instance, rapid recycling of β2 adrenergic receptors and epidermal growth factor receptors might enable these surface proteins on cells to have quick turnover and thereby more readily adjust their sensitivity to hormones and growth factors. This has major effects on; metabolism, cardiovascular function and cell growth/differentiation etc (1-4).
In addition, this kiss-and-run fusion mechanism has implications for how cells regulate the trafficking and localization of essential biomolecules by illuminating previously unknown modes of cell membrane pathology. But the researchers say this novel recycling pathway is operated by a different group of molecular actors, meaning cells have a dedicated machinery for running this version of erasure.
Together, this work reveals the astonishing complexity and plasticity of cellular transport/signaling networks and highlights novel pathways for understanding how cells maximize responsiveness to a variety of cues from their stimulus contexts.
Conclusion
Discovery of this new clathrin-dependent fast endosomal recycling pathway represents a major breakthrough in our understanding of the cellular endocytic and recycling processes. This research reveals a new_membrane fusion mechanism that allows rapid retrieval and recycling of signal receptors: uncovering an unusual ‘kiss-and-run’ process in which the signaling components quickly enter the cell, yet allowing cells to fine-tune their responses to extracellular signals. This discovery could have broad implications for a variety of biological processes, including metabolism and cardiovascular function as well as cell growth and differentiation, declaring yet another battle cry to researchers that we still have much to learn about the intricacies of the eukaryotic cell.
