Roles of the nucleus in leukocyte migration

Abstract

Leukocytes patrol our bodies in search of pathogens and migrate to sites of injury in response to various stimuli. Rapid and directed leukocyte motility is therefore crucial to our immunity. The nucleus is the largest and stiffest cellular organelle and a mechanical obstacle for migration through constrictions. However, the nucleus is also essential for 3D cell migration. Here, we review the roles of the nucleus in leukocyte migration, focusing on how cells deform their nuclei to aid cell motility and the contributions of the nucleus to cell migration. We discuss the regulation of the nuclear biomechanics by the nuclear lamina and how it, together with the cytoskeleton, modulates the shapes of leukocyte nuclei. We then summarize the functions of nesprins and SUN proteins in leukocytes and discuss how forces are exerted on the nucleus. Finally, we examine the mechanical roles of the nucleus in cell migration, including its roles in regulating the direction of migration and path selection.

Human neutrophils ≠ murine neutrophils: Does it matter?

“…The presence of multi-lobed nuclei is considered by some as an attribute that allows neutrophils to traverse tight spaces, as occurs during transmigration through vascular endothelium, because of the flexibility of the nucleus. 36,37 Apparently, high deformability allows human neutrophils to migrate rapidly and to accommodate the variety of vessel sizes encountered. Hypolobulated neutrophils exhibit reduced migratory behavior.…”

“…Certain drugs and some vitamin deficiencies (eg, folic acid, vitamin B 12 ) can cause hypersegmentation of the nuclei of human neutrophils. The presence of multi‐lobed nuclei is considered by some as an attribute that allows neutrophils to traverse tight spaces, as occurs during transmigration through vascular endothelium, because of the flexibility of the nucleus 36,37 . Apparently, high deformability allows human neutrophils to migrate rapidly and to accommodate the variety of vessel sizes encountered.…”