p150Glued

p150Glued, also known as p150Glued dynactin subunit or DCTN1, is a 150-kilodalton subunit of the dynactin complex. In humans it is encoded by the DCTN1 gene and functions as a critical component of the dynein-dynactin motor system that drives retrograde transport along microtubules. The name reflects its origin from the Drosophila gene glued, mutations of which disrupt dynactin function.

Structurally, p150Glued contains an N-terminal CAP-Gly domain that binds microtubules and interacts with plus-end tracking proteins such as CLIP-170 and EB1. A central coiled-coil region enables assembly with other dynactin subunits, supporting complex formation and cargo linkage, while a C-terminal region contributes to interactions within dynactin and with cargo adaptors.

Functionally, p150Glued anchors the dynactin complex to microtubules and facilitates the interaction between dynein and its cargos. It enhances dynein processivity and plays a role in cargo recognition through associations with adaptor proteins. The CAP-Gly domain directs targeting to microtubule plus ends, aiding initial cargo capture, and the complex participates in diverse transport processes, including spindle orientation during cell division and neuronal retrograde transport.

Interactions of p150Glued span the dynactin subunits, dynein heavy chain, and microtubule-binding partners such as CLIP-170 and EB1. It also associates with regulatory factors like LIS1 and NudE and with Rab11-positive recycling endosomes, linking transport to various cellular pathways.

Clinical significance researchers note that DCTN1 mutations cause Perry syndrome, an adult-onset neurodegenerative disorder characterized by parkinsonism, weight loss, and mood disturbances. Other DCTN1 variants have been linked to distal motor neuron diseases and related neurodegenerative phenotypes, underscoring the importance of p150Glued in neuronal cargo transport.