Spectrin repeat proteins in the nucleus

Abstract

Spectrin repeat sequences are among the more common repeat elements identified in proteins, typically occurring in large structural proteins. Examples of spectrin repeat-containing proteins include dystrophin, alpha-actinin and spectrin itself--all proteins with well-demonstrated roles of establishing and maintaining cell structure. Over the past decade, it has become clear that, although these proteins display a cytoplasmic and plasma membrane distribution, several are also found both at the nuclear envelope, and within the intranuclear space. In this review, we provide an overview of recent work regarding various spectrin repeat-containing structural proteins in the nucleus. As well, we hypothesize about the regulation of their nuclear localization and possible nuclear functions based on domain architecture, known interacting proteins and evolutionary relationships. Given their large size, and their potential for interacting with multiple proteins and with chromatin, spectrin repeat-containing proteins represent strong candidates for important organizational proteins within the nucleus. Supplementary material for this article can be found on the BioEssays website (http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html).

Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4

“…These findings most probably indicate a specific role for actinin-4, as actinin-1 has not been detected in the nucleus to date (Babakov et al, 2008). Several proteins that play an important structural role in the cytoplasm are also localized to the nucleus, including SRcontaining proteins such as the spectrins, nesprins, bullous pemphigoid antigen 1 (Bpag1) and nuclear mitotic apparatus protein (NuMA) (Young and Kothary, 2005). These proteins must…”

Nuclear Shape, Mechanics, and Mechanotransduction

“…Several structural proteins are found in the nuclear interior, eg, nucleoplasmic lamin A and lamin C proteins, 12 nuclear actins, 13 nuclear myosin, 14 and nuclear spectrins. 15 Despite the presence of these structural proteins in the nuclear interior, the existence of a structural, forcebearing nuclear matrix throughout the nuclear interior is a matter of open debate. 11,16 …”

“…52 These interactions suggest mechanical or structural function, but none has been determined yet. Interestingly, actin associated proteins such as protein 4.1, 53 myosin, 14 and aII-spectrin 15 have recently been identified in the nucleus as well and might be implicated in movement of DNA within the nucleus. ␣II-Spectrin binds lamin complexes 54 and aids in DNA repair, 55 but the mechanical function of ␣II-spectrin has not been elucidated.…”

Nucleoskeleton mechanics at a glance

“…Lamins A and C also colocalize with proliferation-related proteins, including the activator protein AP-1 (Boban et al, 2010). Short nuclear actins are also involved in many aspects of nuclear function, including transcription and replication (Castano et al, 2010), whereas spectrins located inside the nuclear interior are involved in DNA repair processes (Young and Kothary, 2005). Thus, every important aspect of nuclear function, such as transcription, replication, DNA repair and the control of these processes, is influenced by nucleoskeletal proteins, which possibly serve as scaffolds or regions of localized stiffness.…”