Atlastin

Atlastin

Atlastin is a family of GTPase proteins that play a crucial role in the maintenance and dynamics of the endoplasmic reticulum (ER) network in eukaryotic cells. These proteins are integral to the process of homotypic fusion of ER membranes, which is essential for the formation and maintenance of the tubular ER network.

Structure

Atlastins are characterized by their GTPase domain, which is responsible for binding and hydrolyzing GTP, a process that provides the energy necessary for their function. The protein also contains a middle domain and a C-terminal tail that are involved in membrane tethering and fusion. The GTPase domain is highly conserved across different species, indicating its fundamental role in cellular processes.

Function

The primary function of atlastin proteins is to mediate the fusion of ER membranes. This is achieved through a GTP-dependent mechanism where atlastin proteins on opposing membranes interact, leading to membrane tethering and subsequent fusion. This process is vital for maintaining the continuity and proper function of the ER network, which is involved in protein synthesis, lipid metabolism, and calcium storage.

Clinical Significance

Mutations in the gene encoding atlastin-1 (ATL1) have been linked to hereditary spastic paraplegia (HSP), a group of inherited disorders characterized by progressive weakness and spasticity of the lower limbs. These mutations disrupt the normal function of atlastin, leading to defects in ER morphology and function, which are thought to contribute to the pathogenesis of HSP.

Research

Ongoing research is focused on understanding the precise molecular mechanisms by which atlastin mediates ER membrane fusion and how mutations lead to disease. Studies are also exploring potential therapeutic strategies to correct or compensate for the defective atlastin function in HSP.

Also see

• Endoplasmic reticulum
• GTPase
• Hereditary spastic paraplegia
• Membrane fusion