Transmembrane semaphorins, forward and reverse signaling: have a look both ways

Area of Science:

• Molecular Biology
• Cell Biology
• Developmental Biology

Background:

• Semaphorins are signaling molecules with diverse roles, including axon guidance, immune response, and tumor growth.
• Plexins are the primary receptors for semaphorins, mediating "classical" forward signaling that influences cell migration.
• Semaphorins and plexins can interact in trans and cis, leading to distinct signaling outcomes.

Purpose of the Study:

• To explore the multifaceted signaling capabilities of semaphorins, particularly "reverse" signaling.
• To highlight the roles of semaphorins in both developmental and adult physiological/pathological conditions.

Main Methods:

• Review of existing literature on semaphorin and plexin signaling pathways.
• Analysis of conserved semaphorin signaling mechanisms across species.
• Investigation of cytoplasmic domain interactions in transmembrane semaphorins.

Main Results:

• Semaphorins engage in "forward" signaling via plexins and unique "reverse" signaling through their own cytoplasmic domains.
• Semaphorin reverse signaling is conserved from invertebrates (e.g., fruit fly Sema1a) to vertebrates.
• Vertebrate semaphorins, including class-4 and class-6, exhibit reverse signaling capabilities, potentially involving PDZ-domain interactions.

Conclusions:

• Transmembrane semaphorins possess versatile signaling abilities, acting as both ligands and receptors.
• Semaphorin signaling, including reverse signaling, plays critical roles in development and adult physiology and pathology.
• Understanding these diverse signaling mechanisms is key to deciphering semaphorin functions in various biological contexts.