APPL - DCC-interacting protein 13 | Elisa - Clia - Antibody - Protein

Background

APPL (Adaptor protein, phosphotyrosine interaction, PH domain, and leucine zipper containing 1), also known as DCC-interacting protein 13 (DIP13), plays a crucial role in various cellular processes, including signal transduction, endocytosis, and apoptosis. It is highly conserved across species, indicating its fundamental role in cellular physiology. APPL proteins are known for their interaction with the Deleted in Colorectal Carcinoma (DCC) protein, which is involved in axon guidance and cell survival. These proteins are expressed in a variety of tissues, with particularly high levels in the brain, highlighting their importance in neural development and function.

Protein Structure

APPL proteins have several distinct domains that facilitate their diverse functions:

• BAR (Bin/Amphiphysin/Rvs) Domain: Involved in membrane curvature sensing and binding.
• PH (Pleckstrin Homology) Domain: Binds to phosphoinositides in the plasma membrane, aiding in the localization of the protein.
• PTB (Phosphotyrosine Binding) Domain: Interacts with phosphorylated tyrosine residues on receptor proteins, including the DCC receptor.
• Leucine Zipper Motif: Facilitates dimerization and protein-protein interactions. These domains collectively enable APPL to act as a multifunctional adaptor protein, integrating signals from various pathways and mediating interactions with multiple cellular partners.

Classification and Subtypes

APPL proteins belong to the family of adaptor proteins involved in intracellular signaling and trafficking. There are two main isoforms of APPL in humans: APPL1 and APPL2. These isoforms share significant structural similarity but can have distinct cellular roles and interaction partners. APPL1, in particular, has been studied more extensively and is known to participate in a wide range of signaling pathways.

Function and Biological Significance

APPL proteins are involved in several critical cellular functions:

• Signal Transduction: APPL1 mediates signaling pathways initiated by various receptors, including insulin and adiponectin receptors, influencing metabolic processes.
• Endocytosis: APPL proteins are implicated in the early stages of endocytosis, particularly in the formation of signaling endosomes.
• Cell Survival and Apoptosis: Through their interaction with the DCC receptor, APPL proteins can influence apoptotic pathways, playing a role in cell survival and death.
• Neuronal Development: Involvement in axon guidance and neuronal differentiation highlights their importance in neural development.

Clinical Issues

Dysregulation of APPL proteins has been linked to various diseases:

• Cancer: Abnormal APPL signaling can contribute to tumorigenesis, particularly in colorectal cancer due to its interaction with the DCC receptor.
• Metabolic Disorders: Given their role in insulin signaling, alterations in APPL1 function are associated with insulin resistance and type 2 diabetes.
• Neurodegenerative Diseases: Disruption in APPL function can affect neuronal development and survival, potentially contributing to neurodegenerative conditions.

Summary

APPL proteins, particularly APPL1, play a multifaceted role in cellular signaling, endocytosis, and apoptosis. Their interaction with the DCC receptor and involvement in critical pathways highlight their significance in both normal physiology and disease states. Understanding the detailed mechanisms of APPL function and regulation could provide insights into therapeutic targets for diseases like cancer, diabetes, and neurodegenerative disorders.