Biology subjects

Popp, Y.

Publications and source records attributed to Popp, Y..

3 recordsLinked to original sources

bioRxiv2025

Shaft versus spine localization affects the structural plasticity of glutamatergic synapses

In the early stages of development, most excitatory synapses are formed directly on dendritic shafts. As neurons mature, these sites gradually shift from the shaft to dendritic spines. In fully developed excitatory neurons, the majority of glutamatergic postsynaptic sites containing the postsynaptic density (PSD) molecules reside on dendritic spines. However, some glutamatergic synapses remain as shaft synapses, yet their characteristics have remained unexplored. Here, we show that the molecular composition of the shaft PSDs closely resembles that of spine PSDs. Key components such as AMPARs, NMDARs, CaV1.2 channels, and F-actin interacting proteins, SynGAP, as well as cortactin, are present in comparable amounts in both synapse types. The major distinction between shaft and spine PSDs lies in the lower abundance of the scaffold proteins Shanks and Homer in shaft PSDs. Shaft synapses are not merely passive structures but actively participate in synaptic transmission. Their structure and function are modulated by changes in neuronal activity. Long-term live imaging combined with a cLTP protocol revealed that shaft PSDs were potentiated but rarely underwent a transition to spine synapses. In contrast, during LTD, shaft PSDs were eliminated more frequently than their spine counterparts. Together, these findings highlight excitatory shaft synapses as a distinct, and notably less stable, synapse type.

neuroscience↗

bioRxiv2023

Efficient axonal trafficking of endolysosomes depends on the balanced ratio of microtubule tyrosination and detyrosination

In neurons, the microtubule (MT) cytoskeleton forms the basis for long-distance protein transport from the cell body into and out of dendrites and axon. To maintain neuronal polarity, the axon initial segment (AIS) serves as a physical barrier, separating the axon from the somatodendritic compartment and acting as a filter for axonal cargo. Selective trafficking is further instructed by axonal enrichment of MT post-translational modifications, which affect MT dynamics and the activity of motor proteins. Here, we compared two knockout mouse lines lacking the respective enzymes for MT tyrosination and detyrosination and we found that both knockouts led to a shortening of the AIS. Neurons from both lines also showed an increased immobile fraction of endolysosomes present in the axon, whereas mobile organelles displayed shortened run distances in the retrograde direction. Overall, our results highlight the importance of maintaining the balance of tyrosinated/detyrosinated MT for proper AIS length and axonal transport processes. Summary StatementDespite opposite effects on microtubule dynamics, shifting the balance of microtubule tyrosination/detyrosination in either direction resulted in surprisingly similar defects in axonal organelle transport.

neuroscience↗

bioRxiv2021

Calpains are required for efficient microtubule detyrosination

Detyrosination is a major post-translational modification of microtubules (MT), which has significant impact on MT function in cell division, differentiation, growth, migration, polarity, and intracellular trafficking. Detyrosination of -tubulin occurs via the recently identified complex of vasohibin 1/2 (vash1/2) and small vasohibin binding protein (SVBP). However, there is still remaining detyrosinating activity in the absence of vash1/2/SVBP, and little is known about the regulation of detyrosination. Using cellular and cell-free assays we showed that the calcium-dependent proteases calpains 1 and 2 regulate MT detyrosination. We identified new calpain cleavage sites in the N-terminal disordered region of vash1 using in vitro proteolysis followed by mass spectrometry. However, this cleavage did not affect the detyrosination activity of vasohibin. In conclusion, the regulation of MT detyrosination by calpains occurs via another yet unknown tubulin carboxypeptidase. Importantly, calpains calcium dependency could allow a fine regulation of MT detyrosination. Thus, identifying the calpain-regulated pathway of MT detyrosination can be of major importance for several basic and clinical research and should be focused on in future studies. Summary StatementThe conventional calpains 1 and 2 play an important role in the regulation of microtubule detyrosination in a vasohibin independent way. Thus, they possibly control another still unknown tubulin carboxypeptidase.

cell biology↗