MARCKSlike

MARCKSlike refers to a group of proteins related to MARCKS (myristoylated alanine-rich C kinase substrate) that are encoded by MARCKSL1 and MARCKSL2 in vertebrates. They share core features with MARCKS, including an N-terminal myristoylation site and a highly basic effector domain that can bind phosphoinositides such as PIP2, and a serine-rich regulatory region that can be phosphorylated by PKC.

Functionally, MARCKSlike proteins regulate the actin cytoskeleton and membrane trafficking, influencing cell shape, migration, neurite extension, and vesicle exocytosis. Through PKC-mediated phosphorylation, MARCKSlike proteins detach from the plasma membrane, releasing PIP2 and altering actin dynamics, thereby linking signaling pathways to cytoskeletal remodeling.

Localization and regulation: At rest, MARCKSlike proteins are associated with the plasma membrane via myristoylation and the basic effector domain; upon phosphorylation they translocate to the cytosol. Their activity is controlled by kinases and phosphatases, providing a regulatory connection between signaling events and cytoskeletal remodeling.

Expression and roles: In vertebrates, MARCKSL1 and MARCKSL2 have widespread expression, with notable roles in neural development and cell migration; they may influence neurite outgrowth and synaptic function. In some contexts, MARCKSlike proteins have been implicated in cancer cell motility and metastasis due to effects on the cytoskeleton and vesicle trafficking.

Research and notes: MARCKSlike proteins are studied as models for PKC-regulated actin dynamics and as regulators of PIP2 signaling at the plasma membrane.