Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking.

Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.

Involvement of ROP6 and clathrin in nodulation factor signaling.

The symbiotic association between the legume Lotus japonicus and the nitrogen-fixing bacterium Mesorhizobium loti results in the formation of root nodules. This process begins with the recognition of the rhizobial nodulation factor (NF) by the NF receptors (NFR) at the cell surface of the host roots. The downstream signaling cascades after NFR recognition have not been fully characterized. We recently identified a clathrin heavy chain 1 (CHC1) from L. japonicus as a potential target of the NF signaling cascades. CHC is a known central component in the clathrin-mediated endocytosis (CME) in eukaryotic cells. The CHC1 gene was highly expressed in Rhizobium-infected root hairs and the CHC1 protein was present in cytoplasmic punctate structures near the infection pockets and along the infection thread membrane. Furthermore, expression of a dominant-negative variant of CHC1 or treatment with a chemical inhibitor of CME resulted in impaired phenotypes in the NF signaling, rhizobial infection and nodulation. These findings open a new avenue for future work aiming at understanding the role of endocytosis in NF signaling pathway and rhizobial infection.

Mitochondria and neuroplasticity.

The production of neurons from neural progenitor cells, the growth of axons and dendrites and the formation and reorganization of synapses are examples of neuroplasticity. These processes are regulated by cell-autonomous and intercellular (paracrine and endocrine) programs that mediate responses of neural cells to environmental input. Mitochondria are highly mobile and move within and between subcellular compartments involved in neuroplasticity (synaptic terminals, dendrites, cell body and the axon). By generating energy (ATP and NAD(+)), and regulating subcellular Ca(2+) and redox homoeostasis, mitochondria may play important roles in controlling fundamental processes in neuroplasticity, including neural differentiation, neurite outgrowth, neurotransmitter release and dendritic remodelling. Particularly intriguing is emerging data suggesting that mitochondria emit molecular signals (e.g. reactive oxygen species, proteins and lipid mediators) that can act locally or travel to distant targets including the nucleus. Disturbances in mitochondrial functions and signalling may play roles in impaired neuroplasticity and neuronal degeneration in Alzheimer's disease, Parkinson's disease, psychiatric disorders and stroke.